As a Saudi pharmacovigilance consultancy, we would like to clarify the SFDA requirements for the implementation of QPPV and pharmacovigilance in Saudi Arabia. This is to increase the understanding of the Pharmacovigilance (PV) obligations on the local and multinational pharmaceutical companies. We will also elaborate on scenarios where a local distributor or a scientific office is involved.
In addition, we are going to explain the option to outsource the PV function to a pharmacovigilance consultancy to act as a third party QPPV in KSA on behalf of MAHs.
Pharmacovigilance in Saudi Arabia
In 2005, the Saudi Food and Drug Authority (SFDA) announced the launch of the SFDA pharmacovigilance activities in Saudi by publishing a draft guideline.
Thereafter, SFDA pharmacovigilance regulations rolled out continuously throughout the following few years, including the enforcement of the Qualified Person Responsible for Pharmacovigilance (QPPV) and publishing the SFDA Guideline on Good Pharmacovigilance Practice (GVP).
Now in 2021, the SFDA has reached an advanced level in the applications of pharmacovigilance. The enforcement of drug safety monitoring became more serious with regular inspections on pharmaceutical companies. SFDA firmly checks the integrity of the submitted Pharmacovigilance System Master File (PSMF), Pharmacovigilance Sub-System File (PSSF), Risk Management Plan (RMP), and the QPPV appointment within the drug registration application. In addition, SFDA is leading a countrywide initiative to encourage health care practitioners and patients to report adverse drug reactions (ADRs).
SFDA Pharmacovigilance Regulation
The official pharmacovigilance enforcement took place as follows:
An SFDA circular was issued requesting the industry to submit the aggregate adverse reaction reports (PSURs) to The National Pharmacovigilance and Drug Safety Center, currently named (Saudi Vigilance). This SFDA circular was the first direct enforcement of pharmacovigilance in Saudi Arabia.
SFDA issued a circular marking the first enforcement of QPPV on the pharmaceutical industry.
SFDA issued a circular mandating the Saudization of the QPPV role (to be a job for Saudi nationals only). The circular specified the end of 2016 as the deadline for enforcement.
What is Pharmacovigilance?
It is defined as “The science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem.”WHO
SFDA Pharmacovigilance Guidelines
The first official SFDA Pharmacovigilance Guideline was issued in June 2011 under the name (Saudi Pharmacovigilance Guideline of Registered Medicines). Subsequently, they issued a GVP guideline in 2015 under the name “Guideline on Good Pharmacovigilance Practices (GVP).
The SFDA GVP was the first comprehensive PV reference that came in 499 pages. However, the SFDA wisely applied gradual enforcement to allow sufficient time to understand and absorb such heavy requirements on the industry and obviously the related costs.
Within eleven pharmacovigilance modules, the GVP guideline describes the requirements in each major pharmacovigilance process. They are generally adopted from the EU guidelines but with Saudi-specific requirements. For example, the SFDA requests all international marketing authorization holders to develop and maintain a local pharmacovigilance system in Saudi Arabia. It has to be documented in a file called “Pharmacovigilance Sub-System File (PSSF),” which is needed besides the company’s global PV system “Pharmacovigilance System Master File (PSMF).”
What is meant by pharmacovigilance activities is the process of collection and assessment of safety data, mostly adverse drug events, originating from solicited or spontaneous sources. The whole activity is designed to achieve one objection: to increase the benefit-risk profile of a drug product.
Requirements of Pharmacovigilance in Saudi Arabia
According to the SFDA GVP guidelines, the marketing authorization holder (MAH) is responsible for implementing a compliant pharmacovigilance system. It shall be operated by a QPPV, controlled by a quality system, and documented in special format files (PSMF/PSSF).
We will summarize here the requirements according to the company type:
Local Saudi Distributor (local agent)
Since the ultimate pharmacovigilance responsibility falls on the MA holder, the local distributors are not obliged to hire a QPPV nor implement a PV system. They only need to be trained by the MAH on how to handle safety information, report ADRs, and other PV obligations. They all must be governed by a safety data exchange agreement (SDEA).
The distributor in Saudi shall hire a QPPV and implement a full pharmacovigilance system only when they agree with the MAH to represent them for PV activities in Saudi. They can also outsource it to a pharmacovigilance consultancy office.
Saudi Pharmaceutical Manufacturer
When the Saudi manufacturer is also the MAH for a product, a PV system must be implemented and operated by its own or outsourced QPPV. The PV system represented in the Pharmacovigilance System Master File (PSMF) is sufficient for local Pharmaceutical manufacturers.
International Pharmaceutical Company
With a Scientific Office
Foreign pharmaceutical companies with registered scientific offices must develop and implement a local PV system in Saudi Arabia. This is aside from the one implemented in their global offices. The local PV system shall cover all PV tasks and responsibilities inside the Saudi market to assure their liability for the safety of their registered drugs.
In addition, the MAH must establish a quality management system (QMS) that is adequate for performing pharmacovigilance activities. PV & QMS both can be operated by the QPPV.
The Scientific office also has the option to outsource PV activities to a pharmacovigilance consultancy office.
Without a Scientific Office
When the MAH is having no Saudi based office, (only a local distributor), then it has two options to cover the QPPV obligation:
- Coverage by their local distributor
Where the MAH agrees with the distributor to cover the pharmacovigilance obligations through their registered QPPV. This is a feasable option when the PV function at the local distributor is professional and can meet the SFDA and the PV global office requirments. A simple audit can ensure the reliability before receiving critical and major findings by the authorities.
- Coverage by an outsourced QPPV (Pharmacovigilance Consulting)
Outsourc the PV role to an SFDA licensed pharmacovigilance service provider. This option is the most reliable and feasable when the local distributor is lacking a professional QPPV since the distributors are usually more commercial focused.
Pharmaceutical companies have the option to contract with PV / QPPV service providers. Contracting with a Pharmacovigilance consultancy office is accepted by the SFDA as stipulated in the SFDA GVP guidelines.
Submission of Pharmacovigilance files
In the drug registration application, the MAH must submit the following:
- Pharmacovigilance system
- Pharmacovigilance Sub-System File (PSSF)
Applicable on multinational MAH companies. According to GVP guidelines, the PSSF must be submitted within the first application to the SFDA.
- QPPV and a deputy QPPV appointment files.
- Risk management plan (RMP).
- Risk Minimization Measures, if any.
Qualified Person Responsible for Pharmacovigilance
As part of the pharmacovigilance system, the MAH must appoint a full-time qualified person responsible for pharmacovigilance (QPPV) in addition to a deputy QPPV to work as a backup.
The MAH can either hire its own independent employee (Saudi Pharmacist) or contract with a pharmacovigilance consultancy. The MAH must ensure that the QPPV has sufficient knowledge, training, experience, and qualifications for the performance of pharmacovigilance activities.
The QPPV must meet the minimum requirements as below:
The SFDA named specific QPPV requirements that he or she must carry to be accepted. They are the following certifications and qualifications:
- Bachelor’s degree in pharmacy or medicine
- Licensed by Saudi Commission for Health Specialties (SCFHS).
- Have the skill for the management of pharmacovigilance systems
- Basic training in epidemiology and biostatistics
- Have experience or access to expertise in medicine, pharmaceutical science, epidemiology, and biostatistics.
- Full-time employee or outsourced.
- Available permanently and continuously
- Resides in Saudi Arabia
- Saudi Nationality
QPPV Responsibilities in Saudi Arabia
The SFDA pharmacovigilance guidelines stipulate that the QPPV shall be responsible for establishing and maintaining the pharmacovigilance system. This include:
- Promote, maintain and improve compliance with the legal pharmacovigilance requirements.
- Oversight over the functioning of the company’s quality system, such as standard operating procedures SOPs, CAPAs, documents control, etc.
- Ensuring the propoer conduct of pharmacovigilance activities.
- Acting as the sole pharmacovigilance contact point for the SFDA on a 24-hour basis
- Contact point for pharmacovigilance inspections.
- Establishment and maintenance of Saftey Data Exchange Agreements (SDEA)
- Safety Database operations
- ADRs reporting quality, completeness, and timeliness
- Submission of periodic update reports,
- Annual PV refresher training of company staff
- Creation and maintenance of the Pharmacovigilance system master file PSMF
- Creation and maintenance of the Pharmacovigilance Sub-System File PSSF.
- Submission of all pharmacovigilance documents per SFDA GVP guidelines
- Respond to SFDA inquiries related to the benefit-risk evaluation of a medicinal product
- Ensuring the necessary quality, correctness, and completeness of data submitted to the SFDA;
- Ensuring conduct of pharmacovigilance activities
- Oversee and provide input into the regulatory action plans in response to emerging safety concerns (e.g., variations, urgent safety updates, and communication to patients and healthcare professionals (DHCPs)
- To have an overview of the drugs safety profiles
- To have an awareness of any conditions and obligations related to the products or committed to the SFDA at any stage.
- Aware of and with authority over the content of risk management plans;
- Aware of risk minimization measures;
- Review and approve the protocols of post-authorization safety studies (PASS) conducted in Saudi
- Aware of PASS requested by the SFDA
- Aware of the validation status of the adverse reaction database
- Periodic internal and external audits and archiving of its reports.
QPPV Authority in the Organization
The MAH must provide the QPPV with enough authority to:
- Control the quality system and the pharmacovigilance activities.
- Access to the pharmacovigilance system master file (PSMF) with authority and be aware of any changes.
- Implement changes to the Pharmacovigilance system
- Influence the risk management plans
- Add input to the preparation of the regulatory actions in case of emerging safety concerns.
- Access and receives all relevant information, specifically those related to:
- Emerging safety concerns, product benefit-risk evaluation.
- Clinical trials and studies related to the safety of the drug.
- Information from other sources such as contractual arrangements; and
- Other MAH procedures relevant to the pharmacovigilance system aimed to maintain consistent and compliant organization.
- To be aware of the results and the measures resulted by the frequent review of the quality system.
- To have visibility on compliance information to assure commitments.
- To receive information about scheduled audits and able to initiate new ones.
- To have access to the corrective and preventive plans related to PV.
- To have access to the adverse reactions database.
- In cases of new additions to the MAH products portfolio, such as in acquisitions, the QPPV needs to be aware the soonest to assess potential risks on the pharmacovigilance system.
- To review and approve contract sections related to pharmacovigilance and exchange of safety data.
- In cases of new partnerships with other MAH or Pharmacovigilance consultancy, the QPPV should be aware as early as possible to review the need to receive their pharmacovigilance data, add parts in the contractual agreement, or establish pharmacovigilance agreements.