Quality Management system at Marketing authorization holder organization

 These topic comes under the guidance of Pharmacovigilance:

Introduction:

This module contains guidance for the establishment and maintenance of quality assured Pv system for MAHs for performing their Pv activities; MAHs shall establish and use quality systems that are adequate and effective for the performance of Pv activities.

Structure and processes

A Pv system is defined as a system used by MAH to fulfil its legal tasks and responsibilities in relation to Pv and designed to monitor the safety of pharmaceutical products approved by appropriate licensing authorities in India and to detect any change to their benefit-risk balance. This system should cover MAHs organizational structure i.e. organogram describing Pv personnels’ roles and responsibilities, procedures, processes and resources of the Pv system as well as appropriate resource management, compliance management and record management.

Quality cycle of PV system

The quality system shall be based on all of the following activities:

Quality planning: Establishing structures and planning integrated and consistent processes;

*Quality adherence: Carrying out tasks and responsibilities in accordance with quality requirements

Quality control and assurance: Monitoring and evaluating how effectively the structures and processes have been established and how effectively the processes are being carried out;

Quality improvements: Correcting and improving the structures and processes wherever necessary

Quality objectives for PV

The overall quality objectives of a Pv system are:

Complying with the legal requirements for Pv tasks and responsibilities;

Preventing harm from AEs in humans arising from the use of approved pharmaceutical products within or outside the terms of marketing authorization or from occupational exposure;

Promoting the safe and effective use of pharmaceutical products, in particular through providing timely information about the safety of pharmaceutical product to patients, HCPs and the public;

Contributing to the protection of patients and public health.

Responsibilities for the quality system within an organization

MAH shall have a sufficient number of competent and appropriately qualified and trained personnel for the performance of Pv activities.

For the purpose of a systematic approach towards quality in accordance with the quality cycle, managerial staff in the organization should be responsible for:

Ensuring that the organization documents the quality system;

Ensuring that the documents describing the quality system are subject to document control in relation to their creation, revision, approval and implementation;

Ensuring that adequate resources are available and that training is provided;

Ensuring that suitable and sufficient premises, facilities and equipments are available;

Ensuring adequate compliance management;

Ensuring adequate record management;

Reviewing the Pv system, including its quality system at regular intervals in risk based manner to verify its effectiveness and introducing corrective and preventive measures wherever necessary;

Ensuring that mechanisms exist for timely and effective communication, including escalation processes of safety concerns relating to pharmaceutical products within an organization;

Identifying and investigating concerns arising within an organization regarding suspected nonadherence to the requirements of the quality and Pv system and taking corrective, preventive and escalation action as necessary;

Ensuring that audits are performed;

Assigning roles, responsibilities and authorities to staff members according to their competencies and communicating and implementing these throughout the organization.

Training of MAH personnel for PV

All personnel involved in the performance of Pv activities shall receive initial and continued training. This training shall relate to the roles and responsibilities of the personnel and start within one month of joining. The organization shall keep training plans and records for documenting, maintaining and developing the competences of personnel. Training plans should be based on training needs assessment and should be subject to monitoring.

Facilities and equipment for PV

Achieving the required quality for the conduct of Pv processes and their outcomes is also intrinsically linked with appropriate facilities and equipment used to support the processes. Facilities and equipment should include office space, Information Technology (IT) systems and storage space (electronic). They should be located, designed, constructed, adapted and maintained to suit their intended purpose in line with the quality objectives for Pv.

Facilities and equipment which are critical for the conduct of Pv should be subject to appropriate checks, qualification and/or validation activities to prove their suitability for the intended purpose.

Specific quality system procedures and processes

Compliance management by MAH

For the purpose of compliance management, MAHs shall have specific quality system procedures and

processes in place in order to ensure the following:

Continuous monitoring of Pv data, the examination of options for risk minimization and prevention and that appropriate measures are taken by the MAH (refer Module 6 for detailed information)

Scientific evaluation of all information on the risks of pharmaceutical products as regards patients or public health, in particular as regards adverse reactions in human beings arising from use of the product within or outside the terms of its marketing authorization or associated with occupational exposure

Submission of accurate and verifiable data on all ADRs to the regulatory authority/NCC-PvPI, IPC within the legally required time-limits (refer Modules 2 and 6 for detailed information)

Quality, integrity and completeness of the information submitted on the risks of pharmaceutical products, including processes to avoid duplicate submissions and to validate signals. 

Effective communication with regulatory authority, including communication on new or changed risks, the PvMF (refer Module 1 for detailed information), risk management systems (refer Module 6 for detailed Information), PSURs (refer Module 3 for detailed information) and CAPAs (refer Modules 1& 5 for detailed information).

Record management

The MAH shall record all Pv information and ensure that it is handled and stored so as to allow accurate reporting, interpretation and verification of that information.

As part of a record management system, specific measures should, therefore, be taken at each stage in the storage and processing of Pv data to ensure data security and confidentiality. This should involve strict limitation of access to documents and to databases to authorized personnel respecting the medical and administrative confidentiality of the data. The hard copies should be retained for a minimum of 10 years and soft copies to be stored indefinitely.

Documentation of the quality system

All elements, requirements and provisions adopted for the quality system shall be documented in a systematic and orderly manner in the form of written policies and procedures. For the requirements of documenting the quality system (refer module I for detailed information).

It is recommended that the documentation of the quality system also includes:

Methods of monitoring the efficient operation of the quality system and, in particular, its ability to fulfil the quality objectives;

A record management policy;

Records created as a result of Pv processes which demonstrate that key steps for the defined procedures have been taken;

Records and reports relating to the facilities and equipment including functionality checks, qualification and validation activities which demonstrate that all steps required by the applicable requirements, protocols and procedures have been taken;

Records to demonstrate that deficiencies and deviations from the established quality system are monitored, that CAPA have been taken, that solutions have been applied to deviations or deficiencies and that the effectiveness of the actions taken has been verified.

Critical PV processes and business continuity

The following Pv processes should be considered as critical include:

Continuous safety profile monitoring and benefit-risk evaluation of authorized pharmaceutical products;

Establishing, assessing and implementing risk management systems and evaluating the effectiveness of risk minimization;

Collection, processing, management, quality control, follow-up for missing information, coding, classification, duplicate detection, evaluation and timely electronic transmission of ICSRs from any source;

Signal management;

Scheduling, preparation (including data evaluation and quality control), submission and assessment of PSURs;

Meeting commitments and responding to requests from competent authorities, including provision of correct and complete information;

Interaction between the Pv and product quality defect systems;

Communication about safety concerns between MAHs and licensing authority in particular notifying changes to the benefit-risk balance of pharmaceutical products;

Communicating information to patients and healthcare professionals about changes to the benefit-risk balance of pharmaceutical products for the aim of safe and effective use of pharmaceutical products;

Keeping product information up-to-date with the current scientific knowledge, including the conclusions of the assessment and recommendations from the regulatory authority;

Implementation of variations to marketing authorizations for safety reasons according to the urgency required.

Business continuity plans should be established in a risk-based manner and should include:

Provisions for events that could severely impact on the organization’s staff and infrastructure in general or on the structures and processes for Pv in particular; and  

Back-up systems for urgent exchange of information within an organization, amongst organizations sharing Pv tasks as well as between MAHs and competent authorities

Monitoring of the performance and effectiveness of the PV system and its quality system

Processes to monitor the performance and effectiveness of a Pv system and its quality system should include:

Reviews of the systems by those responsible for management;

Audits;

Compliance monitoring;

Inspections;

Evaluating the effectiveness of actions taken with pharmaceutical products for the purpose of minimizing risks and supporting their safe and effective use in patients.

The organization may use performance indicators to continuously monitor the good performance of Pv activities in relation to the quality requirements. The requirements for the quality system itself are laid out in this Module and its effectiveness should be monitored by managerial staff, who should review the documentation of the quality system at regular intervals, with the frequency and the extent of the reviews to be determined in a risk based manner.

Reviews of the quality system should include the review of SOPs and work instructions, deviations from the established quality system, audits and inspections reports as well as the use of the indicators referred to above.