STANDARD OPERATING PROCEDURE
Title: PHARMACEUTICAL DEVIATION MANAGEMENT
Distribution
Manager, Production.
Work Bench
Quality Compliance Department
Product Development Department
Factory In-Charge
QA Archive (Master Copy)
1. Purpose:
This procedure provides a standardized process for handling quality related unplanned events & GMP deviation.
• To develop a systemic approach for handling quality related failures & GMP deviation.
• To ensure that deviations are recorded and assessed for their impact on product quality, patient safety and regulatory compliance.
• Action is taken to address any immediate risks, including impact on other batches and products.
• Investigation requirements and identification of any corrective and preventive actions (CAPAs) are based upon the level of risk.
Pharmaceutical CAPA Management Workflow
2. Scope:
The process applies to all quality & GMP failures and unplanned deviations in PharmaQMS Ltd. which are related (but not limited) to the following:
Manufacturing Processes/operations (manufacturing, packing, testing, distribution), yield and reconciliation limit.
Facilities including equipment, utilities failure and critical instrument calibration failure.
Equipment/machinery breakdown during operation.
Failure of PLC based system that directly affects product quality
Equipment and facility Operation outside validated ranges
Storage condition of raw and packing materials
Storage period of bulk product
Documentation error affecting product quality.
Product standards
Standard Operating Procedure
Work Instructions including validation protocols.
Incidents impacting GMP & product or material quality
The process does not apply to the following as these are managed separately by individual SOPs:
Out of Specifications (OOS/Atypical) analytical and microbiological results.
Environmental action and alert limit excursions, where these have arisen as a result of laboratory testing
Stability failures/ stability protocols
Customer complaints and adverse events
Equipment/machinery breakdown during routine maintenance
Out of calibration noticed at the time of calibration activity
Recalls
Outside of in-process parameter followed by immediate rectification
Vendor complaints (On line rejection)
Deviations associated with outcome of any non-routine activity or trials.
Where actions have been justified, documented and pre-approved by Quality Assurance e.g. via SOP, BMR, BPR, Analytical Method.
Protocol for Clean Equipment Hold Time Study in Pharmaceuticals
Investigation process will be mandatory in the following instances:
Major/critical deviation/complaints/significant incidents.
OOS
Rejection
Recall
Consecutive 3 time excursions of alert limits.
Any incident agreed by management
3. Definition / Abbreviation:
• Deviation: Deviation is an unplanned departure from SOPs, methods, specifications, protocols, batch records or other official documentation. A deviation may also be defined as a departure from instructions, processes, process specifications or normal conditions or any departure from good manufacturing practice.
• Planned Deviation: A deviation or change to test method, laboratory or manufacturing procedures that has been planned and approved before the process conducted as a part of temporary change. Planned Deviation should be reported before the process. Planned deviations will be handled through the QA approved change control procedures.
The deviations are classified as critical, major and minor. The definition is as under
Critical Deviation - A critical GMP deviation/exception could endanger product safety and/or efficacy due to the use of an inadequate process or controls. Failure of detection would lead to a product recall/withdrawal/serious complaint.
Major Deviation - A major GMP deviation/exception does not directly influence product safety and efficacy but may require remedial action before approval of manufacture or continue to manufacture. This could lead to serious regulatory compliance implications, Major cost to business or adverse comments from inspectors.
Minor Deviation - A minor GMP deviation/exception does not directly influence product safety and efficacy but may have an impact on cosmetic quality. This also includes minor document irregularities. This could lead to Cosmetic pack complaint or Late orders.
Investigation: It is the process of identifying the cause of deviations/unwanted incidents. Purpose of Investigations are:
Identify
Correct
Evaluate product impact / disposition
Prevent similar events from happening in the future;
Pharmaceutical Change Control Procedure
4. Responsibilities:
The Roles and Responsibilities are as follows:
(who observed the incident)
• To notify Section in Charge/Departmental Manager immediately after observing any event.
Initiator (Section in Charge/ Dept. Manager)
• To take any possible immediate actions to contain the event.
• To record the event in log book and batch document.
• To fill the “Deviation and Investigation Form” immediately after “On the spot investigation”.
• To escalate the event to Functional Head
Functional Head or his designee
• To decide in conjunction with Quality Compliance whether the incident is deviation or not and, if confirmed, any subsequent investigation required.
• To ensure proper recording of deviation
• To carry out initial assessment of the incident after collection of required data and ensure recording in batch document.
• To decide on the requirement of assembling investigation team (in consultation with Manager Quality Assurance) for further investigation to find out root cause and define recommendation.
• To invoke CAPA process if require by forming CAPA team.
Head of Quality Compliance or his designee
• Maintain the register for deviation & investigation
• To provide the guidance on whether the incident is a deviation or not
• To participate the initial assessment & follow up of remedial action.
• To assess the severity of deviation and define criticality.
Manager, Quality Assurance
• To approve the initial assessment & remedial action.
• To approve the deviation & investigation
Investigation Leader (Any competent person nominated by Functional Head)
• To lead the investigation and find out the root cause
• To complete investigation within stipulated time.
ACCOUNTABILITY
Head of Quality.
Pharmaceutical Site Master File (SMF)
5. Revision Details:
Sl. No. Version no. Effective date Change History
6. Annexure:
1. Annexure-I: Annexure:
• Annexure-I: Deviation Form
• Annexure-II: Deviation Register
• Annexure-III: Investigation Template
• Annexure-IV: Investigation Register
Pharmaceuticals Annual Product Quality Review (APQR)
7. Procedure:(Management of deviation)
7.1 Observation and notification of Deviation:
7.1.1 If any staff observes any of the incidents (described in scope), he/she will immediately notify the incident to Section in Charge/Departmental Manager.
7.1.2 Section in Charge/Departmental Manager will immediately conduct initial impact assessment and take any remedial action. e.g.
Stopping operation to prevent production of further faulty product,
Segregating material that may be affected.
Immediate correction
7.1.3 Departmental Manager will record the detail incident in the associated log book and/or BMR/BPR in a timely manner. The record must be clear, concise, and traceable and include all relevant details (e.g. time, date and nature of the incident, name of the observer).
7.1.4 Departmental Manager will immediately escalate the event to Functional Head (Head of Department)
7.1.5 Departmental Manager in consultation with Functional Head will determine whether the incident constitutes a deviation based on its potential impact on material/product quality or regulatory compliance.
7.1.6 For the ease of detection they can take the guidance of scopes (Point 2). If there is any doubt as to the potential impact, the event will be treated as a deviation
7.2 Recording of Deviation
7.2.1 If it is determined that the incident constitutes a deviation, then the Departmental Manager will record all the information in section A of Deviation Report Form (Annexure-I).
7.2.2 The Functional Head will decide
if the production/operation should be stopped or not
With proper authorization & justification allow the product to proceed.
7.2.3 Departmental Manager will record the decision in Deviation Report Form. Departmental Manager will assign a unique reference number (obtained from Quality Compliance Office) to the Deviation Form.
7.2.4 The number will be derived from Deviation register (Annexure-II). Deviation register will be maintained in both hard copy and Microsoft Excel based spreadsheet.
7.2.5 Deviation Form number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: DRyy/Departmental Code/xxx.
For example: DR15/PRO/001.
The first two alphabets shall stand for Deviation Report
Next two numeric characters shall stand for year code 15 shall denote year 2015.
Next character is slash (/), followed by departmental code (To be collected from SOP for SOP)
Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Deviation Report no DR15/PRO/001 and second DR15/ENG/002, third DR13/PKG/003 and so on.
7.2.6 The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
7.2.7 If incident implicates a batch then the unique reference number is to be recorded in related batch documents.
7.2.8 The deviation must be recorded with the following information:
A unique reference number
The date on which the deviation was first identified
Name of person recording the deviation
The identity (Batch No.) of any batch or batches implicated by the deviation
A description of the deviation
The identity of any process, equipment or system implicated by the deviation
Initial actions taken
7.2.9 Functional Head will ensure that all relevant data/information is gathered to allow an initial assessment of the deviation.
SOP of Procedure for Training in Pharmaceuticals
7.3 Assessment of risk
7.3.1 Departmental Manager along with Quality Compliance Manager and any other expert in this field (i.e. Engineering Manager/Compliance Manager/Quality Control Manager/Microbiology Manager) will assess the impact of the deviation considering the following issues (section B in Annexure-I) and will propose a remedial action within 1 day of recording the deviation:
Patient/customer risk & product efficacy
Quality Implication (strength, identity, purity and stability)
Effect on regulatory compliance
Impact on any batch (es) immediately affected.
Impact on any other batch(es)/processes which may be affected, considering any other areas/sites
Current location and status of any implicated batch (whether the implicated batch is on the market or within control).
Any remedial action taken/required
Detection point of failure (detected by chance/detected during checking/detected at the point of error)
7.3.2 The initial assessment may result in wider implications than originally identified e.g. more batches than just the batch the deviation was detected on.
7.3.3 Quality Compliance Manager will assess the risk of deviation considering the above and categorize or prioritize the event as:
Critical
Major
Minor
7.3.4 The aim of this categorizations are to determine the:
Priority for resolving the deviation
The time scale for addressing the deviation
Communication details & person to whom incident is to be communicated (if required).
7.3.5 Non conformity which is not detected through any standard process or detected only by chance will be treated as critical/major deviation. In all cases where the deviation relates to, or may implicate product already in the market place, will also be treated as critical.
7.3.6 Critical deviation will be immediately escalated to Manager, Quality Assurance. Manager, Quality Assurance will communicate the matter to Managing Director and other stakeholders accordingly.
7.3.7 If requires Manager, Quality Assurance will communicate the matters to Contact Manufacturer and collect their recommendation for the correction of the product.
7.3.8 Quality Compliance Manager in consultation with other Technical /Quality Experts will provide a recommendation/ remedial action to ensure that any adverse condition arising from the deviation are controlled and pose no further risk.
7.4 Determine Root Cause Investigation Requirements
7.4.1 Manager, Quality Assurance in consultation with Head of department will assess whether root cause investigation is required.
7.4.2 Root cause investigation is required where there is a risk to patient/ customer safety or serious regulatory compliance issues assigned through severity assessment in section 7.3.3. . For example:
The severity of deviation is Critical/Major.
Remedial actions have not fully mitigated the risk
The deviation is a recurrence
7.4.3 If root cause investigation is not required, Manager, Quality Assurance will give a rationale and the deviation process can be progressed toward to point close.
7.5 Perform root cause investigation
7.5.1 The investigation will be conducted as per process described in point 7.9.
7.5.2 The key output from this investigation will be a statement of actual root cause or most probable cause of the deviation and recommendation with timescale to address root causes.
7.5.3 After completion of the investigation, a copy of the investigation will be attached with the deviation report.
7.6 Identify Corrective and Preventive Action (CAPA)
7.6.1 On the basis of the severity of investigation, the Head of department jointly with Manager, Quality Assurance & Quality Compliance Manager will decide on the requirement to invoke CAPA process and develop Corrective and Preventive action to address the root cause identified in section 7.5 and prevents recurrence of happening in future.
7.6.2 In case of CAPA process not applicable, this process should be closed with the comments and authorization by Manager, Quality Assurance.
7.6.3 CAPA will not be required if Manager, Quality Assurance confirms the followings:
If the deviation categorized as minor.
Implementation of identified CAPA is no longer applicable-for instance the root cause relates to equipment that has been replaced, or is planned to be replaced as part of an existing approved action.
Remedial actions taken address the root cause
The risk related to recurrence is low
7.6.4 If CAPA process is applicable, Head of Department will identify competent person to be a CAPA Leader to implement the CAPA objectives. CAPA leader will follow the formal CAPA process as per SOP: Corrective and Preventive Action Handling Procedure
7.6.5 The Deviation Handling process will be closed when the CAPA triggered from this process is approved.
7.7 Handling of deviation implicated batch
7.7.1 No batch will be released until the deviation is closed.
7.7.2 All actions required to assure the quality of any impacted batches must be identified, agreed by the Quality Compliance, and completed prior to batch release
7.7.3 The copy of closed deviation report and investigation report must be filed with associated batch document (if implicated with any batch) during batch release.
7.7.4 Manager, Quality Assurance has ultimate authority to take decision on progression or release after completion of all actions.
7.8 Time limit, Follow up and Management Review
7.8.1 If investigation is not required deviation is to be closed within 7 days of initiation.
7.8.2 For deviation associated with investigation will be closed within 15 days of deviation initiation.
7.8.3 Initiator will coordinate the implementation of recommended/remedial action within agreed timeframe.
7.8.4 Quality Compliance will ensure that deviation has been effectively closed within the agreed timeframe. After closing Quality Compliance Manager will update the deviation tracker & register and archive the hard copy of original deviation form. A copy to be provided to attach with the relevant document such as validation protocol.
7.9 Handling of Investigation:
7.9.1 Investigation will be triggered to address any unexpected discrepancy from different interfaces:
Critical/Major Deviation
Critical/Major market compliant
Any GMP Quality incident
Recall, reject and Reprocess
7.9.2 Functional Head (Head of Department) and Manager, Quality Assurance will jointly decide where the investigation is required.
7.9.3 If root cause investigation is required, the Functional Head(Head of Department) will check the criticality of incident (critical/major/minor) as defined in the interface to determine the scale of investigation e.g. extent of investigation team, amount of structure for problem solving, level of documentation, requirement of resources or capital budget etc.
7.9.4 The Functional Head (Head of Department) will nominate an Investigation Leader & other members of investigation team who will conduct the investigation. Generally Departmental Manager of impacted area will be selected as Investigation leader.
7.9.5 For the complex investigation, team should be cross functional composing the members of Quality Unit, Engineering and any other Technical Experts.
7.9.6 The team will take a unique reference number of investigation from Quality Compliance Office. Quality Compliance Officer will log the details in the investigation register (Annexure- IV).
7.9.7 All investigation will be conducted through this form (Annexure-III: Template of an investigation report).
7.9.8 Investigation Report numbers are assigned by Quality Compliance. Investigation Report number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows:
IRyy/Departmental Code/xxx.
For example: IR15/GB/001.
The first two alphabets shall stand for Investigation Report
Next two numeric characters shall stand for year code 15 shall denote year 2015.
Next character is slash (/), followed by departmental code (to be collected from SOP for SOP)
Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Investigation Report no IR15/PRO/001 and second IR15/ENG/002, third IR15/PKG/003 and so on.
7.9.9 The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
7.10 The team will collate the facts and data in consultation with relevant personnel and document.
7.11 Investigation team will prepare a report of investigation within the time line. All steps & findings will be recorded in the report.
7.12 The key aim of the investigation is to identify the root cause or most probable cause of the deviation incident.
7.13 Where the identification of actual or most probable root cause is not possible, the risk associated with uncertainty is to be assessed & recoded with adequate control.
7.14 The maximum time for the identification of root cause is 15 working days after recording of incident.
7.15 Investigation report will be approved by Functional Head (Head of Department) and Manager, Quality Assurance.
