// June 21, 2023

Protecting patients from substandard and falsified medicines through post-marketing surveillance

APEC supply chain dialogue meeting

Substandard and falsified (SF) medical products remain one of the most significant public health concerns at national, regional, and global levels, and post-marketing surveillance is an essential part of the solution, panelists agreed during an April 26 session of the Asia-Pacific Economic Cooperation (APEC) forum’s Medical Product Supply Chain Dialogue, co-hosted by the U.S. FDA and USP in Rockville, Maryland. The panel was titled “Securing the Downstream Supply Chain: Post-marketing Surveillance.”

Post-marketing surveillance to monitor a medical product’s quality, safety and efficacy profile following regulatory marketing authorization involves regular and ad hoc spot check inspections, and collecting and analyzing data on real-world use of the medicine. It helps identify any emerging, potential quality and safety concerns, risks or adverse effects and events, including the potential for SF medical products to enter the supply chain. It also facilitates appropriate management of such issues, when they arise, to ensure ongoing safety and effectiveness of medicines for their intended use.

National and regional regulatory authorities are responsible for preventing, detecting, and responding to SF medical products that fail to meet quality specifications and could pose health risks to patients and consumers. However, the complexity of today’s global supply chains for medical products and porous national borders make it easier for potential SF products to enter distribution and circulation. The “last mile” of the downstream supply chain can pose particularly significant challenges, including logistical complexities associated with certain global geographies.

LMICs need more resources for post-marketing surveillance

Low- and middle-income countries (LMICs) often encounter numerous hurdles in effectively executing post-marketing surveillance programs. One of the main challenges is the limited number of staff available to conduct the necessary activities required for such programs to be effective. Another challenge arises from the fact that a significant portion of the available workforce may lack the necessary qualifications to conduct crucial tasks.

Further, the ever-evolving nature of emerging issues, such as SF medical products, necessitates additional training on new approaches, tools, technologies and implementation of robust post-marketing surveillance programs. Also, data available for regulatory decision-making are sometimes sporadic, inconsistent, and unenforceable, making it difficult for regulatory authorities to take action and make informed decisions about the quality, safety and efficacy of medical products already on the market.

Regulatory maturity requires capability building

While the relative “maturity level” of national regulatory systems sometimes lags behind peer countries in certain geographies, the World Health Organization (WHO) Global Benchmarking Tool (GBT) is used by WHO to objectively evaluate regulatory systems and their maturity. The tool helps identify strengths and areas for improvement, formulate institutional development plans, prioritize interventions, and monitor progress. The GBT evaluates the overarching regulatory framework and component regulatory functions through sub-indicators grouped into nine cross-cutting categories.

Approximately 70% of national regulatory authorities are at maturity level 1 and 2, representing relatively weak regulatory systems, and WHO has intensified efforts to facilitate achievement of maturity level 3 (ML3) status, representing a stable, well-functioning and integrated national regulatory system, per WHO GBT requirements. The Promoting the Quality of Medicines Plus (PQM+) program, implemented by USP, helps strengthen regulatory systems and WHO maturity levels in LMICs. In 2022 alone, six countries achieved ML3/ML4 for medicines and vaccines regulatory systems, leading to a call for increased adoption of risk-based approaches to post-marketing surveillance.

During the panel discussion, WHO’s Rutendo Kuwana, team lead, Incidents and Substandard/Falsified Medical Products, commended the Republic of Korea’s Ministry of Food and Drug Safety for its November 2022 achievement of maturity level 4 (ML4), which is the highest level in WHO’s classification of regulatory authorities for medical products.

Action needed to address SF medicines

Uneven global access to medical products and regional demand that can outstrip supply during a public health emergency such as the COVID-19 pandemic can create economic incentives for deliberate falsification of medicines. Panelist Thomas Kubic, principal of Pharmaceutical Security Consulting and former CEO of the Pharmaceutical Security Institute, noted that in 2021 there was an “alarming…50% increase in incidents of counterfeit medicines infiltrating the legitimate supply chain.” Earlier this year, WHO issued a global call to action to prevent, detect and respond to incidents of SF medicines. To address the issue during the pandemic, USP produced a suite of resources targeting SF vaccines and treatments.

Addressing the potential for SF products in particular, panelist Kuwana emphasized that “identifying causes and implementing effective risk controls through regulatory practice can aid in the minimization of SF medical products available in the market.” Noting the identification in recent months of SF medicines in Gambia, Indonesia and Uzbekistan impacted by confirmed or suspected contamination of cold syrups with diethylene glycol and ethylene glycol that led to the deaths of numerous children, Kuwana emphasized that proper responses to such incidents requires coordination between health emergency teams and national health authorities to determine if the issue at hand is actually a SF medical product. Risk assessment, communication, and mitigation through post-marketing surveillance are also important steps in the process. However, a potential lack of access to adequate quality control laboratories can inhibit corrective actions, such as product recalls.

During the panel discussion, participants spotlighted opportunities to enhance sub-regional, regional, and continental cooperation and collaboration to strengthen regulatory requirements for pre-market evaluation and post-market control, facilitate the exchange of information on SF medical products, and enable joint assessments, timely investigations, and appropriate regulatory responses. To address the global issue of SF medicinal products, it is essential to conduct routine post-marketing surveillance using a risk-based approach, and to promote regional and international cooperation, despite potential challenges, panel discussion participants generally agreed.

Panelist P.T. Thomas, professor and executive dean, Faculty of Health and Medical Sciences at Taylor's University, Malaysia, underscored the “importance of combining good distribution practices with post-marketing surveillance to eliminate substandard or falsified medicines.” In Malaysia, licensing is mandatory for all parties in the distribution chain, and holograms are used to prevent counterfeit products.

Comprehensive post-marketing surveillance activities in the Philippines were highlighted by panelist Raymond Sia, food-drug regulation officer IV, Field Regulatory Operations Office, Food & Drug Administration, Republic of the Philippines. “We employ various strategies including pharmacovigilance, supply chain inspection, market surveillance and monitoring, rapid response, enforcement, and effective communication, collaboration, information sharing, and education and training,” Sia said.

Toolkit supports post-marketing surveillance

The U.S. FDA led a collaboration within APEC economies – in conjunction with WHO, USP, regulators, and academia – to create a Supply Chain Security Toolkit for Medical Products aimed at maximizing available global resources for securing the supply chain and combatting SF medical products. The toolkit offers comprehensive international guidelines, technical documents, examples, and tools to support the implementation of post-marketing surveillance programs, including sections that address quality testing, sampling drug products, and global evidence-based data on poor-quality products.

By implementing effective post-marketing surveillance programs, regulatory authorities can take necessary actions and work together to protect public health and safety, including through the issuance of safety alerts in response to adverse events or other safety signals, and recalling potential SF drugs when necessary.