The Critical Role of National Reference Material Systems in Pharma
The COVID-19 pandemic caused significant disruptions to global supply chains for pharmaceutical intermediates. This has made import independence for critical drug components and active substances a priority for many nations.
Russia's import substitution strategy includes establishing a new national system for drug and active pharmaceutical ingredients (API) reference standards, to be developed by the the National Center of Standard Samples under the State Institute of Drugs and Good Practices (SIDGP).
Pharmaceutical Applications of Reference Standards
Reference standards (RS) are primarily used by quality control departments at pharmaceutical manufacturing facilities during various production stages. Essentially, they serve as benchmarks for testing active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs) on key quality indicators: identification and quantitative analysis. Developing control methods using reliable, precise, and sensitive physicochemical techniques together with reference standards enhances quality oversight by both manufacturers and regulators.
Furthermore, drug reference standards may be applicable in related fields. For example, they are used in pharmacokinetic studies, therapeutic drug monitoring to adjust medication regimens, and in chemical-toxicological investigations to determine causes of poisoning or fatal outcomes. Reference standards are also used in environmental monitoring at pharmaceutical plants and in drug development research.
Development and Supply of Reference Standards
The process varies by country. For example, in the United States, this area is managed by the USP (U.S. Pharmacopeia), operating under the FDA. This organization develops and produces reference standards (RS) and identification tests for the food industry, pharmaceuticals, and veterinary medicine. Similarly, the European Pharmacopoeia (Ph. Eur.) functions under the EMA (European Medicines Agency). It develops, adopts, and approves reference standards while ensuring regulatory oversight. Thus, in both the EU and the U.S., all activities related to reference standards are consolidated within specific organizations. These agencies not only supply their domestic markets but also export standards globally. Additionally, there are reference standards produced by private companies, which are distributed worldwide without restrictions. These are often used for compounds not covered by major pharmacopeias but still essential for industry needs.
The Reference Materials System in Russia
The circulation of reference standards (RS) as such is limited in Russia. At the beginning of 2020, only about 60 RS units were registered in Russia. For comparison, the USP (United States Pharmacopeia) catalog of reference standards for pharmaceutical substances, excipients, impurities, food additives, and pharmacopeial reagents is nearly 60 times larger. Federal Law No. 61 'On the Circulation of Medicines,' in addition to pharmacopeial RS and reference standards of the Russian State Pharmacopoeia, permits the use of international RS, reference standards from foreign pharmacopeias and manufacturers, as well as chemical substances of the required purity grade. Taking advantage of this, pharmaceutical manufacturers primarily import USP or European Pharmacopoeia reference standards.
Risk of reference standards import for the pharmaceutical production
The domestic industry remains vulnerable to global disruptions, as exemplified by the 2020 lockdowns. Currency Volatility Impact Fluctuations in the ruble exchange rate directly affect the cost of imported reference standards. Inherently Higher Costs U.S. and European reference materials carry premium pricing, as distributors incorporate their margins into the final unit cost. For large manufacturers, annual expenditures on reference materials can reach hundreds of millions of rubles, typically requiring immediate payment. Challenges in Supply Chain Oversight Monitoring intermediary activities presents significant difficulties, creating potential vulnerabilities. Extended Lead Times Delivery periods for imported reference materials can range from several weeks to six months, creating production planning challenges.