Quality Management System for Reference Material Handling

The Quality Management System (QMS) for reference material (RM) manufacturing integrates pharmaceutical and managerial practices to ensure high-quality output. Strict adherence to standards and conformity testing is essential. QMS harmonization faces challenges due to divergent international quality requirements, as well as economic and cultural differences. The first RMs were developed in the USSR in 1961. Today, RMs are referenced in most major pharmacopoeias, though a universally accepted classification system remains absent. ISO/TR 10989:2009 proposes categorizing RMs into pharmacopoeial standards and manufacturer-produced RMs.

International guidelines (e.g., ICH Q7) establish RM development rules, including the use of in-house primary standards when official ones are unavailable. According to GOST ISO Guide 30-2019, RMs are classified as RM, CRM (Certified Reference Material), and matrix RM based on defined characteristics, metrological traceability, and intended use.

RM and CRM properties are determined through characterization, homogeneity assessment, and stability testing. Stability studies follow homogeneity confirmation and factor into certified value uncertainty calculations. Russia applies ISO 9000-series standards and GOST R ISO 17034—2021, which define RM producer competency. To validate measurement traceability, manufacturers undergo voluntary QMS certification at the National Metrology Institute (NMI), confirming technical competence.

Reference Material Producers (RMPs) must implement a QMS, employ qualified personnel, maintain production controls, develop procedures, use verified methods and measurement tools, confirm RM stability and homogeneity, and document sample certifications. QMS requirements (per GOST R ISO 9001-2015 and 17034-2021) can be met by either establishing a new system or adapting an existing one, provided all regulatory clauses are satisfied.

Managerial and technical requirements encompass: document control, audits, production oversight, personnel and contractor management, equipment and method validation, plus nonconformance and complaint handling. Russian RMs are categorized by recognition level: state, interstate, industry, corporate, and COOMET standards. Certified RMs must demonstrate metrological traceability, include certificates, and comply with GOST R ISO 17034-2021.

GOST R ISO 17034 further specifies production process requirements: planning, quality control, storage, method application, homogeneity/stability evaluation, characterization, data analysis, documentation, and post-market monitoring. CRMs additionally require metrological traceability and uncertainty evaluation for certified values.

The absence of an RM producer recognition system may compromise quality, making its implementation under the State RM Service a priority. Aligning producers with international standards, QMS certification, and introducing "certified RM" status will enhance measurement accuracy, comparability, and global acceptance. We recommend: - Developing a unified international framework - Adopting ISO 17025 standards - Systematizing RM purity assessment methods - Facilitating inter-organizational knowledge exchange - Staff training programs - Participation in accreditation schemes (e.g., ILAC) These measures will standardize RM production and control, enabling global recognition.