Quality Management System SOP


1.               PURPOSE:

Quality Risk Management (QRM) is the overall and continuing process of properly managing potential or arising risks from different operations, activities and discrepancies, to product safety, Identity, strength, purity and quality, throughout the product's life-cycle in order to optimize its benefit–risk balance. It is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.


2.               SCOPE:

This procedure is applicable for all the departments to perform the risk assessment of quality management, facility, equipment, utilities, production, laboratory control, stability testing, packaging and Labeling at all units of Natco Pharma limited, Pharma division, Kothur.


3.               REFERENCE:

GQA/039-03 and ICH Q9 – Quality Risk Management.


4.               DEFINITION:

§  Risk: The combination of the probability of occurrence of harm and the severity of that harm.

§  Risk Assessment: A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.

§  Risk Initiation: Identifying the risk using suitable technique such as brain storming process.

§  Quality Risk Management Program: The systematic application of quality management policies, procedures and practices to the tasks of assessing, controlling, communicating and reviewing risk.

§  Risk Analysis: The estimation of the risk associated with the identified hazards.

§  Risk Control: Actions implementing risk management decisions.

§  Risk Mitigation: Systematic reduction in the extent of exposure to a risk and/or the likelihood of its occurrence. Also called risk reduction.

§  Risk Reduction: Actions taken to lessen the probability of occurrence of harm and the severity of that harm.

§  Risk Evaluation: The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk.

§  Risk identification: The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.

§  Risk Communication: The sharing of information about risk and risk management between the decision maker and other stakeholders.

§  Risk Summary /Conclusion: It is summary report of observations / mitigation which has high RPN with appropriate actions proposed, target date and responsible person to reduce the identified risk.

§  Risk Review Report: Review or monitoring of output/results of the risk management   process considering (if appropriate) new knowledge and experience about the risk.

§  Detectability: The ability to discover or determine the existence, presence, or fact of a hazard.

§  Severity: A measure of the possible consequences of a hazard.

§  Systems & procedures:  The term “System and procedures” represents any cGMP related procedures and practices meant to be implemented through a manual or computer based system (Example: Implementation of SAP, LIMS, Vendor evaluation SOP etc.)

§  Critical processes / Unit Operations: The processes and operations which determines or  contribute to the quality parameters of a product, where it is perceived to be critical irrespective of the status of being validated and verified routinely through in-process and or QC checks. (Aseptic processes, Sterilization, Isolator technology, etc.).


5.               RESPONSIBILITY:

§  Personnel from User department along with the applicable cross functional teams shall initiate the Risk Assessment and prepares the summary report along with the mitigation plans and actions (If any).

§  The cross functional department heads / Designee shall review the risk assessment report and responsible for completion of actions as per timelines.

§  The Quality assurance team member ensuring the completeness of identified action item.

§  Head Quality Assurance or his designee shall authorize the risk assessment.

§  All cross functional department heads / Designee and Head Quality Assurance or his designee shall be responsible for the implementation and compliance of this procedure


6.               FREQUENCY:

§  As and when required.



7.               PROCEDURE:

7.1           Initiation of Risk Management Program:

The risk initiation shall be carried out at the following stages but not limited to this.


7.1.1     Quality Management:

a)      Documentation: To determine the desirability of and/or develop the content for SOPs, guidelines, etc.

b)     Training and education: To determine the appropriateness of initial and/or ongoing training sessions based on education, experience and working habits of staff, as well as on a periodic assessment of previous training.

c)      Quality defects: To provide the basis for identifying, evaluating and communicating the potential quality impact of a suspected quality defect, complaint, trend, deviation, critical investigation, out of specification result, etc:

To facilitate risk communications and determine appropriate action to address significant product defects, in conjunction with regulatory authorities (eg: Recall).

d)     Periodic review: To understand monitoring data (Ex: To support an assessment of the appropriateness of revalidation or changes in sampling). 

e)      Change management/change control: To evaluate the impact of the changes on the availability of the final product.

To evaluate the impact on product quality of changes to the facility, equipment, material, manufacturing process or technical transfers. Need of risk assessment shall be identified on below criteria.

Change Type

Risk Assessment


Risk Assessment shall be performed for Critical changes


Risk Assessment need to be performed for Major changes, if risk Assessment not required for any Major changes, justification shall be provided.


Risk Assessment not required for Minor changes.


7.1.2     Development:

a)      To enhance knowledge of product performance over a wide range of material attributes (eg: Particle size distribution, moisture content, flow properties) processing options and process parameters.

b)     To assess the critical attributes of raw material, solvents ,active pharmaceutical ingredients(API) starting materials, APIs, Excipients or packaging materials.

c)      To establish appropriate specifications, identify critical process parameters and establish manufacturing controls.

d)     To decrease variability of quality attributes.

§  Reduce product and material defects.

§  Reduce manufacturing defects.

e)      To assess the need for additional studies (eg: bioequivalence, stability) relating to scale up and Technology transfer.





7.1.3     Facilities, Equipment and Utilities:

a)      Design of facility/equipment: To determine appropriate zones when designing buildings and facilities. e.g:

§  Flow of material and personnel.

§  Minimize contamination

§  Pest control measures.

§  Prevention of mix-ups.

§  Open versus closed equipment.

§  Clean rooms versus isolator technologies.

§  Dedicated or segregated facilities/equipment.

To determine appropriate product contact materials for equipment and container (eg: selection of stainless steel grade, gaskets, and lubricants).

To determine appropriate utilities (eg: steam, gases, power source ,compressed air, heating,       ventilation and air conditioning (HVAC), Water).

To determine appropriate preventive maintenance for associated equipment.

b)     Hygiene aspects in facilities: To protect the product from environmental hazards, including chemical, microbiological and physical hazards.(eg: determining appropriate clothing and gowning, hygiene concerns).

c)      Qualification of facility/equipment/utilities: To determine the scope and extent of qualification of facilities, buildings and production equipment and/or laboratory instruments.

d)     Calibration/preventive maintenance: To set appropriate calibration and maintenance schedule.

7.1.4     Materials management:

a)      Starting material: To assess differences and possible quality risk associated with variability in starting (eg: age, route of synthesis.).

b)     Use of material: To determine whether it is appropriate to use material under quarantine.

c)      Storage, logistics and distribution conditions: To assess the adequacy of arrangements to ensure maintenance of appropriate storage and transport conditions (eg: Temperature, humidity, container design.)