Regulatory Affairs Networking Dinner: Strengthening Africa’s Pharmaceutical Sector Through Harmonization and Reliance

The Imperative for & Challenges with Regulatory Reliance & Harmonization Procedures by the Biopharmaceutical Industry – Dr. Angeline Achoka, Senior Regulatory Affairs Manager Sub Saharan Africa, AstraZeneca

Dr. Achoka introduced reliance as a process where a national regulatory authority in one jurisdiction can take into account and give significant weight to assessments performed by another national regulatory authority or trusted institution in reaching its own regulatory decision. The relying authority remains independent, responsible, and accountable regarding the decision. She outlined the adoption of risk-based approach to medicines registration, emphasizing on the utilization of work-sharing, unilateral reliance pathways, and regionalization models to enhance access to safe, quality, and effective health products. She underscored the complexity in navigating post-approval changes, a major challenge within the product management lifecycle in Africa.

She delineated the types of reliance in existence:

• Bidirectional/Horizontal reliance activities: In this pathway, regulatory bodies mutually rely on each other’s assessments to make informed decisions. This is evident in various joint assessment activities, where agencies combine resources to conduct various regulatory activities.
• Unidirectional/Vertical reliance activities: In this, a regulatory authority with resource constraints leverages the expertise of a better resourced regulatory authority and trusted organization, to make informed decisions.

 Underscoring the critical role of reliance in regulating health products in the modern pharmaceutical landscape characterized by limited resources, globalization, and growing public health demands, she argued that, if effectively implemented, African states and all key stakeholders stand to gain various benefits.

Reflecting on various examples in her extensive experience in the regulatory affairs field, she discussed some challenges to implementation and opportunities for fostering regulatory reliance, including:

• Marketing different versions of the product in different markets
• Overly redacted inspection and assessment reports due to confidentiality laws
• Hesitancy from some assessors to use these types of pathways
• National requirements that need reassessments
• Need for agreed-upon metrics to determine if these pathways are reliable.
• Transparency on what to do when there is a safety, quality or regulatory concerns and an agency used reliance pathway in making its regulatory decisions.
• Incentives for the agency on whom another agency relies.

Dr. Achoka emphasized the pivotal role of data as the cornerstone of all reliance pathways emphasizing the importance of data in regulatory decision making as a key piece safeguarding public health.

Regulatory Reliance & Harmonization Pathways in the MD/IVD space: Opportunities & Next Frontiers – Steve Kipkoti, Senior Regulatory Affairs Manager, Medtronic

Steve Kipkoti highlighted key distinctions between the pharmaceutical and medical device industries, stressing that while both are crucial in healthcare, they diverge significantly in innovation, technology, compliance, product range, and adverse events. Medical technology share similarities with information technology in aspects such as scientific basis, innovation, intellectual property, research and development, and technology lifecycle. The regulation of a product as a medical device depends significantly on its intended use. For example, a heart rate measuring device intended for diagnosing medical conditions requires regulation while that intended for fitness and general wellness does not. Medical devices encompass a broad spectrum, ranging from simple tools like thermometers to complex robotic surgery devices.

In defining a medical device, he highlighted inclusivity of software, in-vitro reagents, implants, or appliances, noting that the scope of action may be aided by pharmacological, metabolic means, or immunological.

He discussed the steps involved in the market authorization of a new medical devices, which encompass:

• Establishing the product by identifying the intended use, indication and duration for use, and target patient population.
• Verification of the product as a medical device based on the above.
• Identifying its classification, which is a significant determinant of the regulatory pathway and level of evidence required.
• Developing valid scientific evidence such as clinical data or animal studies appropriate to the potential risk of the product.
• Preparation of pre-market submission depending on the type of device.

He underscored the importance of shared responsibility between governments and manufacturers in ensuring timely access of safe, effective, and quality medical devices. Governments are tasked with establishing and periodically revising policies and regulations to accommodate technological advancements while manufacturers must uphold quality standards during manufacturing. The regulation of medical devices is driven by factors such as an aging population, increasing chronic diseases, rapid MedTech innovation, and government initiatives to promote public well-being and reduce healthcare costs. In Africa, the regulation of medical devices remains a challenge, with only a handful of countries having established formal regulatory processes. Most countries lack formal regulatory processes, creating opportunities to establish and develop regulatory frameworks and pathways. Within the regulatory landscape of the medical device industry, significant barriers include resource constraints, as well as the lack of political commitment. Steve Kipkoti commended the efforts of the Pharmacy and Poisons Board (PPB) in regulating medical devices, particularly noting its involvement in the Medical Device Single Audit Program (MDSAP) Through its recognition under MDSAP, the PPB can rely on audits conducted by Stringent Regulatory Authorities (SRAs) and can participate in joint audits with SRA regulators. This participation streamlines the certification process for medical technology manufacturers, enabling them to supply to SRAs more efficiently.

The absence of common regulatory frameworks and challenges related to regulator resources impede patient access to innovative and life-saving medical devices. Kipkoti stressed the imperative to enhance government efficiency through collaborative regulatory convergence and reliance among African regulatory authorities. This entails information sharing, joint audits, and leveraging experiences to adopt international best practices, thereby reducing costs, time to market, and the risk of technical trade barriers.

He further acknowledged the absence of or limited regulations for telehealth solutions in the continent with need for multisectoral collaboration to bring these up as they were needed. In the interim he proposed the adoption of international standards and regulations as guardrails before local regulations would be in place.

This he pointed to be critical to ensure that lack of regulations does not pose a risk to the public who use these technologies. Steve Kipkoti concluded his speech by urging the delegates to be autodidactic, stressing the importance of self-learning and posing the right questions.

Health Product Security: Regulatory System Challenges and New Frontiers with Reliance Procedures- Dr. Juliet Konje Senior Programme Manager, Africa Partnerships & Growth U.S Pharmacopeia

Dr. Konje commenced her speech by describing the benefits of reliance for the different stakeholders involved i.e., patients, healthcare providers, pharmaceutical manufacturers, and national regulatory authorities. Manufacturers benefit from streamlined regulatory processes, facilitating efficient management of submissions and predictable timely approvals. Patients and healthcare providers gain access to safe, effective, and quality medical products in a timely manner. National regulatory authorities are empowered to utilize resources efficiently, thereby enhancing regulatory systems. She elaborated on the principles of reliance and stressed the importance of trust in fostering effective reliance pathways. Using the EAC-MRH pathway as an illustration, Dr. Konje highlighted the detrimental impact of mistrust on reliance pathways’ efficiency.

Despite the East African Community’s shared language and national anthem, the EAC-MRH initiative had not fully realized its potential due to the absence of trust among other teething challenges among member countries. When charting the path towards reliance, it’s imperative to establish trust from the grassroots level. The path to reliance entails several stages, beginning with national regulatory authorities making independent decisions. This foundation extends to collaborative efforts such as work-sharing, where regulatory tasks are jointly conducted by competent authorities. Further progression involves the implementation of regional reliance mechanisms, followed by unilateral and mutual recognition agreements with stringent regulatory authorities.

She highlighted new frontiers in reliance pathways, highlighting that reliance is currently mainly focused on GMP certifications, market authorizations, and product approvals, overlooking potential benefits in other areas.

Priorities for Biopharmaceutical Industry & Regulatory Agencies’ Investments to Strengthen Regulatory Reliance in Kenya & Africa: Lifecycle Approach to Regulatory Reliance – Dr. Robert Miano Superintendent Pharmacist and Qualified Person for Pharmacovigilance at Imperial Managed Solutions East Africa and Chairperson, Kenya Association of Pharmaceutical Industry (KAPI) Trade and Policy Committee

Dr. Miano kicked off his speech with an overview of WHO guidelines on good reliance practices  and encouraged the delegates to explore additional resources on the WHO e-learning platform. He highlighted Kenya’s progress in achieving reliance, particularly through its involvement in regional harmonization initiatives like the East Africa Community Medicines Regulatory Harmonization (EAC-MRH). Outlining initiatives undertaken by the Pharmacy and Poisons Board (PPB) to improve regulatory efficiency and reliance, he emphasized capacity building as a primary focus. These efforts include induction training for new assessors, on-the-job training, participation in assessment activities with WHO, EAC, or IGAD, and bilateral engagement with sister regulatory agencies. Kenya employs reliance procedures for marketing authorization and emergency use authorization in various situations where:

• Product should have been evaluated and listed as a WHO Prequalified Product or Emergency Use Listed (EUL) product.
• The applicant should have granted authorization for access of assessment reports.
• Products registered by WHO listed agencies may be considered through the reliance mechanism.
• Any bilateral cooperation between Kenya and foreign governments.
• Products in which the drug substance/API used has a valid CEP or it’s Prequalified by WHO.

The PPB has also adopted reliance approaches to the certification of API/FPP manufacturers and CROs/BE centers in;

• Unilateral reliance involving desk reviews for companies located in, and under the oversight of, Stringent regulatory Authorities whereby inspection reports and identified documents are reviewed under desk reviews.
• Unilateral recognition of certifications by listed/recognized NRAs/countries
• Joint inspections/Work sharing within the East African Community member states. Work sharing within IGAD member states is under establishment
• Abridged inspection

The Pharmacy and Poisons Board utilizes unilateral reliance in GMP inspections, acknowledging decisions made by other regulatory authorities or institutions to streamline its own decision-making process, particularly in emergency use authorizations. The pharmaceutical industry assumes a pivotal role in fortifying reliance by actively engaging in regulatory harmonization forums and fostering collaboration through industry associations like the Kenya Association of Pharmaceutical Industry (KAPI). They contribute to capacity building efforts by allocating resources for training programs and supporting financial needs. Additionally, they facilitate the exchange of best practices and adapt practices to suit the local context, thus contributing significantly to the enhancement of reliance mechanisms.