The NAFDAC Good Pharmacovigilance Practice Guidelines in Nigeria

This article will be focused on notable provisions of the National Agency For Food and Drug Administration and Control (NAFDAC) on Good Practices of Pharmacovigilance, which the World Health Organization(WHO) has defined Pharmacovigilance as the science and  activities relating to the detection, assessment, understanding and prevention of  adverse effects or any other medicine-related problem. 

The ultimate goal of  pharmacovigilance is to improve the safe and rational use of medicines, thereby  improving patient care and public health. The National Agency for Food and Drug Administration and Control (NAFDAC)  ACT Cap N1, LFN 2004 empowers the Agency to control and regulate the  manufacture, importation, exportation, distribution, advertisement, sale and use of its  regulated products.

This mandate requires the Agency to ensure the quality, safety  and efficacy of all regulated products. The Agency therefore has developed NAFDAC Good Pharmacovigilance Practice  Regulations to ensure safety of medicinal products that it regulates. 

The NAFDAC regulations describe the obligations of the Certificate of Registration Holder to set up a system for pharmacovigilance in order  to collect, collate and evaluate information about suspected adverse reactions of  products it puts into the Nigerian market. The ultimate goal is to ensure that  medicinal products put into the Nigerian market are safe and effective, and continue  to provide a satisfactory balance between their benefits and risks. 

The obligations concerned with the monitoring of adverse reactions occurring in clinical trials do not  fall within the scope of pharmacovigilance activities, as described in these guidelines.  The relevant obligations in safety reporting for clinical trials are as prescribed in  NAFDAC Good Clinical Practice Regulations. 

What are the objectives of the guidelines?

These guidelines are intended to help all stakeholders comply with the provisions of  the GVP regulations. They provide detailed guidance for Certificate of Registration  holders on establishing and maintaining a pharmacovigilance system including its  quality management, pharmacovigilance system master file, adverse reaction/event reporting, risk management, post authorization safety/efficacy studies, risk  communication and pharmacovigilance audit. The first edition of these guidelines published in 2016 was adapted from the  European Medicines Agency’s guidelines for Good Pharmacovigilance Practices  (GVP), that provides the most comprehensive description of best practices in safety  monitoring and reporting for Certificate of Registration holders. 

This first review is in compliance to the NAFDAC Quality Management System  requirement for continuous improvement. This document is to be used in conjunction with other existing relevant medicinal  product statutes in the country. The good practices outlined below are to be considered  general guides, and they may be adapted to meet individual needs as long as the Certificate of Registration holder achieves compliance  with regulatory objectives.

What is the scope of the guidelines? 

These guidelines apply to all entities that have authorisation to put  medicinal products into the Nigerian market. 

Who is an eligible certificate of registration holder under the guidelines?

The Certificate of Registration holders include but are not limited to :-

– NAFDAC license  holders;

– Individuals, 

-Public and private institutions,

– Manufacturers, importers and  donors of medicinal products. 

These guidelines apply to products whose authorisation to market or distribute include  requirements for active safety monitoring. 

What are the product categories covered by the GVP regulations?

The products covered by the GVP regulations include but are not limited to: 

• Products developed wholly or to a greater extent in other regions. 

• Products with less than ten (10) years post marketing experience elsewhere  or five (5) years in Nigeria.
• Advanced therapeutic products such as tissue, cell or gene based products .
• Products that are subject to risk management plans in any other country .
• Orphan medicinal products 
• Products that received accelerated or conditional marketing approval in any  country .
• Products for use solely in special populations such as children and the elderly.
• Products that act via the immune system such as cytokines and monoclonal  antibodies.
• CNS therapeutic products such as medicines for epilepsy, neurodegenerative  diseases, antipsychotics, antidepressants 
• Any other product based on benefit risk assessment of the Agency .The Agency may also require a Certificate of Registration holder to adhere to these  guidelines where the Agency identifies safety concerns in the course of post  marketing surveillance. This does not discharge the Certificate of Registration holder  of the responsibility of monitoring the safety of all its medicinal products through  the established pharmacovigilance systems required by the Agency.

What exactly is a Pharmacovigilance system as mentioned under the guidelines?

 -A pharmacovigilance system is defined as a quality system used by  the Certificate of Registration Holder to fulfill its regulatory   responsibilities in relation to pharmacovigilance. It is designed to monitor   the safety of authorized medical products and detect any change to their   benefit-risk balance. 

– A pharmacovigilance system is characterized by its structures, processes and outcomes. It covers organizational structure, responsibilities,   procedures, processes and resources of the pharmacovigilance system as   well as appropriate resource management, compliance management and   record management. 

What are the quality objectives of a pharmacovigilance system?

The overall quality objectives of a pharmacovigilance system are: 

• Complying with the legal requirements for pharmacovigilance tasks and responsibilities; 
• Preventing harm from adverse reactions in humans arising from of authorized medicinal medicinal products within or outside the terms of Certificate of Registration such as off  label use, misuse, abuse or medication errors which result in  ADR or from occupational exposure;  
• Promoting the safe and effective use of medicinal products, in particular through providing timely information about the safety of medicinal products to patients, healthcare professionals and the public; and 
• Contributing to the protection of patients and public health. 

What are the general principles guiding the execution of quality objectives under the guidelines?

With the aim of fulfilling the overall quality objectives, the following  principles should guide the design of all structures and processes as well  as the conduct of all tasks and responsibilities: 

• The needs of patients, healthcare professionals and the public  in relation to the safety of medicines should be met. 
• Top management should provide leadership in the  implementation of the quality system and motivation for all  staff members in relation to the quality objectives. All persons within the organization should be involved in and support the  pharmacovigilance system on the basis of task ownership and responsibility to a degree according to their tasks and assigned responsibilities. 
• All persons involved with the entire organization should  engage in continuous quality improvement. 
• Resources and tasks should be organized as structures and  processes in a manner that will support the proactive, risk proportionate, continuous and integrated conduct of  pharmacovigilance. 
• All available evidence on the benefit-risk balance of medicinal  products should be sought and all relevant aspects, which  could impact on the benefit-risk balance and the use of a  product, should be considered for decision-making. 
• Good cooperation should be fostered between Certificate of  Registration Certificate of Registration holders , the  Agency, public health organizations, patients, healthcare  professionals, learned societies and other relevant bodies in  accordance with the applicable legal provisions.

What are the provisions of the guidelines on Personnel ?

-A sufficient number of competent and appropriately qualified and  trained personnel should be available for the performance of  pharmacovigilance activities. Their responsibilities should include  adherence to the principles defined in the guidelines.

– Managerial staff should be responsible for: 

• Ensuring that the organization documents the quality system  as described under the guidelines.
• 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  equipment are available ; 

• Ensuring adequate compliance management ;  

f.Ensuring adequate record management ; 

• Reviewing the pharmacovigilance system including its quality  system at regular intervals in a risk- based manner to verify its effectiveness  and introducing  corrective and preventive measures where necessary; 
• Ensuring that mechanisms exist for timely and effective  communication of safety concerns relating to medicinal  products within the organization; 
• Identifying and investigating concerns arising within the  organization regarding suspected non-adherence to the  requirements of the quality and pharmacovigilance systems  and taking corrective and preventive action as necessary; 
• Ensuring that audits are performed . 

-In relation to the management responsibilities described  above, top management within the organization should  provide leadership through: 

• Motivating all staff members’ based on shared values, trust  and freedom to speak and act with responsibility and through  recognition of staff members contributions within the  organization; 
• Assigning roles, responsibilities and authorities to staff  members according to their competencies and communicating  and implementing these throughout the organization. 

Training of personnel for pharmacovigilance 

– Achieving the required quality for the conduct of pharmacovigilance  processes and their outcomes by an organization is intrinsically linked  with the availability of a sufficient number of competent and  appropriately qualified and trained personnel.

-All personnel involved in the performance of pharmacovigilance  activities should receive initial and continued training. This training  should relate to the roles and responsibilities of the personnel.

– The organization should 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. 

– The training should support continuous improvement of relevant  skills, the application of scientific progress and professional  development and ensure that staff members have the appropriate  qualifications, understanding of relevant pharmacovigilance  requirements as well as experience for the assigned tasks and  responsibilities. 

– All staff members of the organization should receive and be able to seek information about what to do if they become  aware of a safety concern. 

– There should be a process in place within the organization to check  that training results in the appropriate levels of understanding and  conduct of pharmacovigilance activities for the assigned tasks and  responsibilities. 

– The system should also be able to identify unmet  training needs, in line with professional development plans agreed for  the organization as well as the individual staff members. 

– Adequate training should also be considered by the organization for  those staff members to whom no specific pharmacovigilance tasks  and responsibilities have been assigned but whose activities may have  an impact on the pharmacovigilance system or the conduct of  pharmacovigilance.

– Such activities include but are not limited to those  related to clinical trials, technical product complaints, medicinal  information, terminologies, sales and marketing, regulatory affairs,  legal affairs and audits. 

Facilities and equipment for pharmacovigilance 

-Achieving the required quality for the conduct of pharmacovigilance  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 (electronic) storage space.

– Facilities and equipment should be located, designed, constructed,  adapted and maintained to suit their intended purpose in line with the  quality objectives for pharmacovigilance and also be  available for business continuity. 

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

– There should be processes in place to keep awareness of the valid  terminologies in their valid versions and to keep the  IT systems up-to-date accordingly. 

Specific quality system procedures and processes by Certificate of Registration holders For the purpose of compliance management

-Certificate of Registration holders should have specific quality system  procedures and processes in place in order to ensure the following: 

• The continuous monitoring of pharmacovigilance data, the  examination of options for risk minimisation and prevention  and that appropriate measures are taken by the Certificate of  Registration holder; 
• The scientific evaluation of all information on the risks of  medicinal 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 Certificate of Registration or associated with occupational  exposure ; 
• The submission of accurate and verifiable data on serious and  non-serious adverse reactions to the Agency within the legally  required time-limits ; 
• The quality, integrity and completeness of the information  submitted on the risks of medicinal products, including  processes to avoid duplicate submissions and to validate  signals ; 
• Effective communication by the Certificate of Registration  holder with the Agency, including: 
• Communication on new or changed risks , 
• The pharmacovigilance system master file , 

iii. Risk management systems , 

• Risk minimization measures , 
• Periodic safety update reports , 
• Corrective and preventive actions,

vii. Post-authorisation safety studies .

• The update of product information by the Certificate of  Registration holder in the light of scientific knowledge; 

• Appropriate communication of relevant safety information to  healthcare professionals and patients.