he Certificate of Pharmaceutical Product (CPP) is an essential part of almost every dossier submission for most regulators around the globe. No other regulatory document has influenced regulatory discussions and connected regulators globally as profoundly as the CPP. But despite the WHO Scheme’s original goal in 1969 of establishing the CPP as a tool to enable reliance practices and reduce/replace (parts of) the assessment by CPP-requesting National Regulatory Authorities (NRAs), regulatory procedures and CPP acceptance have varied significantly among countries.

Established by the WHO Certification Scheme on the quality of pharmaceutical products moving in international commerce, the CPP was the first-ever regulatory reliance tool. Issued by National Regulatory Authorities (NRAs), the CPP confirms the Quality, Safety, and Efficacy (QSE) of pharmaceutical products. It assures that the product has been fully evaluated by the issuing authority and meets its standards, reducing the need for additional reviews by requesting authorities, which may lack the infrastructure for a full QSE review.

The articles and interviews in this Special Section will explore how the CPP and its historical lessons can guide future reliance practices to provide global access to new therapies.

Trusted Regulatory Reliance Tool for Decades

For decades, the CPP has been vital in facilitating the international medicines trade, ensuring that only medicines that are approved by reference authorities enter other markets, and aiding regulatory activities throughout the product lifecycle.

The CPP has become indispensable for registering medicinal products in more than 100 countries and is a mandatory part of regulatory requirements for new product submissions and lifecycle maintenance or for the import of medicines around the world.

The WHO’s model certificate template, widely adopted by both issuing NRAs and requesting NRAs, has cemented the CPP’s role. Its importance was reaffirmed in the 2021 update to the WHO Certification Scheme and the WHO Good Reliance Practice Policy, which explicitly recognizes the CPP as a reliance tool, urging NRAs to integrate it into their assessment processes.

Current Trends and Challenges

Some NRAs have misinterpreted the CPP’s role, treating it more as an administrative document, with little or no public health or regulatory relevance, rather than leveraging the valuable information it contains to use it as a reliance tool to shorten the review and approval timeline.

Additionally, and curiously, some NRAs demand further authentication/legalization of this inherently legal document!

Concurrently with and indirectly related to the growing administrative challenges imposed by the number of CPPs required for many regulatory activities, more regulatory agencies have begun allowing the electronic submission of registration dossiers. This shift has led CPP-issuing NRAs such as the EMA, MHRA, and US FDA to introduce, and CPP-requesting NRAs to accept, electronic CPP (eCPP), in line with the WHO Certification Scheme and electronic signature regulations.

Enhancing Utilization of eCPP

Despite WHO being supportive of eCPP implementation and efforts of eCPP-issuing authorities to promote this practice, adoption of electronic certificates varies among CPP-requesting NRAs. Fortunately, improvements have been observed in recent years, and based on the experiences since the introduction of the eCPP, several considerations will further enhance its use:

• NRAs should integrate eCPPs with digital systems for dossier submission and review, incorporating e-signatures.
• International security standards for electronic signatures should be enforced to ensure document authenticity, eliminating the need for additional legalization (e.g., Apostille).
• Adoption of WHO’s CPP template should be expanded to ensure regulatory convergence and facilitate consistent information sharing.

(See related article: Industry Survey: Global Acceptance and Use of EMA’s eCPPs.)

The use of eCPPs can significantly benefit the regulatory process by:

• Increasing collaboration and trust among regulators
• Enhancing document security and reducing falsification risks (e.g., through establishment of the authenticity verification tools)
• Modernizing and harmonizing administrative content
• Accelerating submissions and access to medicinal products
• Ensuring regulatory compliance and a sustainable supply of medicines
• Simplifying global CPP processing.

In addition, using digital technologies such as eCPPs contributes to conservation of environmental resources.

Experts agree that the practice of accepting eCPPs should continue and should be expanded. To support the current CPP framework and guide its modernization, the IFPMA has developed a training toolkit and position papers, aligned with WHO recommendations.

What is the Value of CPP/eCPP in the Future of Global Health?

As the global pharmaceutical landscape evolves, the CPP remains crucial for ensuring the safe and timely availability of quality medicines worldwide. Three key attributes contribute to the CPP’s longevity as a reliance tool: its widespread use; its trusted status; and its transparent and harmonized content.

Moving forward, stakeholders should explore how the enhancement of these three attributes could support efficient regulatory reliance practices globally.

One proposal is for the WHO, as the Certification Scheme’s founding institution and an advocate for efficient regulatory reliance, to collaborate with both issuing NRAs and requesting NRAs to further explore the CPP’s potential to address the identified challenges. The pharmaceutical industry could partner in such activity by piloting new concepts and co-developing optimal solutions.

Recent research (reports here and here) suggests that sharing harmonized assessment information among Reference Authorities and relying authorities may facilitate the adoption of reliance practices. Key considerations include:

• Improving methods for sharing nonpublic assessment information
• Enhancing communication channels
• Creating secure platforms for data sharing
• Developing standards and practices for evaluating Reference NRA decisions, including a common template to demonstrate and assess product sameness.

Many of these practices have already been implemented to some extent through the utilization of the CPP/eCPP: from the common CPP template for sharing the information on product attributes and assessments, to the use of secure digital solutions and platforms with the introduction of the eCPP.

The next step is to build on these experiences and further enhance the CPP. Considering its valuable and enduring use over the years, perhaps the first step could be a revision of the CPP template to include additional information that would better suit the needs of regulators and support the more efficient implementation of regulatory reliance.

Industry is open to engaging with WHO, NRAs, and other stakeholders to develop fit-for-purpose solutions.