DDReg Pharma

DDReg Pharma

The Future of Certificate of Suitability

The Certificate of Suitability (CEP) to the monographs of the European Pharmacopoeia (Ph. Eur.) plays a crucial role in verifying the quality standards of active pharmaceutical ingredients (APIs). Issued by the European Directorate for the Quality of Medicines (EDQM), the CEP serves as evidence that an API complies with the rigorous quality requirements outlined in the relevant Ph. Eur. monograph. This article explores the significance, application process, key components, and recent updates of the CEP.
The Importance of CEPs
The CEP holds international recognition and is accepted as proof of API quality in numerous countries beyond Europe. By including a CEP in a marketing authorization application (MAA), the assessment process for regulatory authorities is simplified as they can rely on the evaluation conducted by the EDQM. The primary focus of the CEP is to ensure API quality, including aspects such as purity, impurity limits, and manufacturing processes. It applies to a broad range of APIs, encompassing synthetic chemicals, biotechnological products, and herbal substances. The EDQM conducts regular inspections and re-evaluations of CEP holders to ensure ongoing compliance with quality standards. Confidentiality of information contained in the CEP is maintained, and accessible only to regulatory authorities and the certificate holder. The CEP provides flexibility to MAA applicants by allowing them to reference the CEP instead of submitting extensive API quality data. The EDQM collaborates with pharmacopoeial experts to develop and update monographs, ensuring that the CEP remains aligned with the latest scientific and regulatory advancements. Ultimately, the CEP facilitates global harmonization of API standards, promoting international trade and the availability of safe and high-quality medicines worldwide.
Acceptance and Global Scope
CEPs are recognized by the 38 member states of the Pharmacopoeia Convention, extending their acceptance beyond the European Union. Additionally, several countries outside Europe, such as Australia, South Africa, and Saudi Arabia, acknowledge the validity of CEPs. As a result, CEPs have gained wide-ranging international acceptance.
Types of Certificates
CEPs come in various forms depending on the specific requirements of the API:
  1. Simple Chemical Certificate
  2. Simple TSE or Herbal Certificate
  3. Double Certificate (Chemical + TSE)
  4. Certificate for Chemical Purity and Sterility
  5. Certificate for Chemical Purity and Sterility + TSE
Responsibilities and Application of CEPs
API manufacturers are responsible for obtaining the CEP and submitting it to competent authorities as part of the authorization procedure. The EDQM, located in Strasbourg, serves as the issuing authority for CEPs. The marketing authorization holder (MAH) and the CEP holder both benefit from the clarity provided by this document regarding the content-related details of a CEP.
Key Components of a CEP
A chemical CEP includes essential elements for comprehensive documentation of API quality:
  • Subtitle (optional): Specifies additional details such as polymorphic form, particle size, or specific claims like “sterile” or “pyrogen-free,” subject to evaluation by the EDQM.
  • Information on Sites: Provides details about the manufacturer of the API, CEP holder, intermediates, and various processing activities.
  • Impurities: Outlines limit values for different impurity categories, ensuring compliance with dosage form and maximum daily dose requirements.
  • Container Closure System: Describes primary and secondary packaging requirements for the API.
  • Other Quality Criteria: Specifies quality criteria for water used in oral dosage forms, with microbiological quality assessment depending on specific requirements.
  • Retesting Period: Determines the need for a retesting period based on stability data and includes it in the CEP if necessary.
  • Components of Animal or Human Origin: Declaration of components of animal or human origin and estimation of transmissible spongiform encephalopathy (TSE) risk, if applicable.
Recent Updates and Transition to CEP 2.0
CEP 2.0 brings several changes to enhance efficiency and transparency:
  • Electronic Document Format: CEPs will be transformed into electronic documents with a digital signature, facilitating sharing and inclusion in MAAs.
  • Changes in Numbering and Access Declaration: The numbering system of CEPs will be modified, and the access declaration on the document will be replaced by a letter of access.
  • Revised Information Reporting: Reporting of chemical purity, herbal drug preparations, and substance quality will undergo revisions, replacing previously reported technical information with annexed specifications and approved additional methods.
  • Reporting Water Quality: CEPs will include information on the quality of water used in substance synthesis, providing a more comprehensive understanding of the manufacturing process.
  • On-line Public Certification Database: The public CEP database on the EDQM website will have new features, including Loc ID and EMA SPOR/OMS Org for CEP holders, and the history of finalized procedures for each CEP application.
  • Authorities Database: The authorities database will mention EMA SPOR/OMS Org and Loc ID for CEP holders and manufacturing sites. Under suitable confidentiality agreements or Memorandum of Understanding (MoU), access may be granted to regulatory authorities beyond Ph. Eur. 
  • Information Sharing: CEP holders will be required to share suitable information in addition to the CEP itself, strengthening communication and transparency with customers.
  • Reduction of CEP Revisions: If their content remains unchanged then CEPs will no longer be revised, impacting the numbering system and renewal process.
  • Stepwise Implementation: CEP 2.0 will be implemented gradually, with new CEPs and renewals receiving the new look while existing CEPs can switch to the new format.
  • Training and Guidance: Webinars, training sessions, and guidance materials will be provided to support users during the transition to CEP 2.0.
The Certificate of Suitability to European Pharmacopoeia Monographs (CEP) plays a vital role in ensuring API quality and compliance with Ph. Eur. standards. Widely recognized internationally, the CEP simplifies the regulatory assessment process and promotes global harmonization of API standards. Recent updates and the upcoming transition to CEP 2.0 aim to enhance efficiency, transparency, and information sharing, ultimately benefiting both CEP holders and regulatory authorities.
References ad Further Reading
  • EDQM. Certification European Directorate for the Quality of Medicines and HealthCare
  • EDQM. Mission and Organisation European Directorate for the Quality of Medicines and HealthCare
  • EDQM. The Inspection Program European Directorate for the Quality of Medicines and HealthCare
  • EDQM. CEP 2.0 European Directorate for the Quality of Medicines and HealthCare