Guide to Good Storage and Distribution Practices for Pharmaceuticals

1. Compliance with Good Practices – Ticket to Company’s Success Quality Director, R-Pharm GC T.M. Vyazmina

2. GOOD STORAGE PRACTICE (GSP) • Storage and transportation of drug products (DP) take place at all stages of handling the DP, from their production to their delivery to the patient, and they must comply with Good Storage Practice (GSP) and Good Distribution Practice (GDP). • Good Storage Practice: • Sets requirements to storage conditions necessary to ensure quality, safety and effectiveness of drug products • Describes special activities used for storage and transportation of DP including requirements to personnel, premises and facilities, storage, returned goods, transportation and product recall • Applies to participants of storage, transportation and distribution processes Good Storage Practice (GSP)

3. GOOD DISTRIBUTION PRACTICE (GDP) • Sets requirements towards conditions of storage and transportation of DP, • Is necessary for the assurance of quality, safety and effectiveness of DP • Applies to distributors and manufacturers of DP • Is aimed to minimize the risk of appearance of falsified, substandard, counterfeit DP in civil circulation The purpose of GDP is compliance with set conditions for storage, transportation and distribution of DP. Observance of these regulations ensures the control of supply chain of DP GSPandGDPare closely related with Good Manufacturing Practice (GMP) and ‘cold-chain’ management GDP Good Distribution Practice

4. What does GDP and GSP compliance serve for? • 1. Compliance with the requirements of good practices is an essential condition set by regulatory bodies aimed to ensure the quality of product and patients’ safety (meeting regulator’s expectations). • 2. Compliance with good practices allows to use the instruments of Pharmaceutical Quality System starting with quality risk management, which is also an instrument of effective resource management, an effective source of information necessary for taking objective and well-reasoned decisions in the issues related to commerce, quality, distribution of company’s forces. • 3. Compliance with GDP, GSPrequirements is a good business practice for a company, which allows it to become the leader in its field and improves its attractiveness in the market. • 4. If the requirements of good practices are not observed, it may lead to: • rejection of the product by regulatory bodies; • damage to patient’s health; • disruption of product supply; • business losses.

5. Pending issues to be resolved in the nearest future • Tentatively, the amount of distributors in Russia is about 3 000 companies • No obligatory requirements to distributors regarding obtaining the GDP, GSP compliance certificates as contrasted with the necessity for DP manufacturers to receive GMP certificate.It puts distributors and manufacturers of DP in different conditions. • Currently, no GDP inspectorate in the RF andEAEU • It would be logical, in our opinion, to delegate the function of inspections for the purpose of licensing of pharmaceutical activities (Roszdravnadzor) and the function of inspections for the purpose of licensing of drug products production (Ministry of Industry and Trade) to the same executive authority. Such approach would allow to regard the inspections from the same point of view. • State Institute of Drugs and Good Practices has the resources, competencies, trained personnel for the inspection of all distributors in regard to their compliance with GDP, GSP practices for their further licensing and obtaining a GDP-, GSP-compliance certificate.

6. Pending issues to be resolved in the nearest future • Higher education institutions do not prepare specialists in the field of pharmaceuticalmanagement, in particular, specialists for distributors’ quality assurance. • No certification required for distributors’ senior quality officers in comparison to the certification of qualified persons of DP manufacturers • Currently, the following normative documents are in effect in the RF: • Resolution of the RF Government as of 22 December, 2011 No.1081 “On Licensing of the Pharmaceutical Activity” • Order of the Ministry of Labour of Russia as of 22 May, 2017 No.428n “On the Approval of Professional Standard “Specialist in the Field of Pharmaceutical Activity Management”. • Type of economic activity:

7. Questions to the audience Who can help resolve GDP-related issues? Which country/organization has been successful in the creation of an inspectorate on the international level? Which organization in Russia and the EAEU is responsible for the confirmation of GSP-, GDP-compliance?

8. List of typical GDP non-compliances Motor transportation (by cold-storage vehicles) Audits confirm that distributors do own validated vehicles. It means that the formal side of GDP requirements is observed. Yet physical checkups of vehicles used for transportation of DP show that non-validated vehicles are used along with validated ones. Transportation companies giving motor transport for outsourcing do not have formalized requirements towards drivers in regard to the latter’s actions in case of emergencies with cold-storage vehicles.

9. Hardships of implementation of GSP, GDP requirements In order to ensure ‘cold-chain’ conditions for temperature-sensitive DP in the airports of the RF, documents in support of GDP, GSP are needed, which would oblige the airports to operate within the same regulatory framework as manufacturers and distributors do.

10. Hardships of implementation of GSP requirements • Relative humidity norm for the storage of drug products is still unchanged in the State Pharmacopoeia of the RF, XIV edition. OFS.1.1.0010.18 Storage of drug products: • GM.1.1.0010.18Storage ofdrug products: • “Drug products are stored with relative humidity of 60 + 5% depending on the corresponding climate zone (I, II, III, IVA, IVБ), unless otherwise indicated in the ND.”

11. List of typical GSP non-conformities • Use of different approaches to the management of business processes in logistics: • In hard copy; • On electronic media (automated directory and documentation systems) • puts manufacturers/ distributors in unequal situation. • In most cases, paper-based systemis non-compliant with quality system requirements: • The system of identification of product location in a warehouse has a lot of drawbacks compared to an automated identification system for product location; • No traceability in warehouse documents (logbook, shelf card, other) in regard to the assigning of product location, its physical placement for storage, its shipping

12. Measuring instrumentation for control of ‘cold-chain’ mode • Currently, the following tendencies exist in regard to measurement instruments used for the control of temperature mode during storage and transportation of medical immunobiological drugs within the ‘cold-chain’ system (temperature loggers and temperature indicators). Discussions are currently being held about their registration as medical devices, which is an absolutely incorrect approach. • General metrological requirements such as: • Approval of the type of measurement instruments, • Their state calibration and calibration, • are sufficient for the use of measurement instruments, which are currently in the market. Medical devices are any tools, devices, instruments, equipment, materials and other items used for medical purposes separately or in combination with each other, as well as with other appliances, required for the designated use of the indicted items including special software, and which were intended by the manufacturer to be used for the prevention, diagnostics, treatment and medical rehabilitation of illnesses, monitoring of the state of human body, medical researches, reconstruction, replacement, change of the anatomical structure or physiological bodily functions, prevention or interruption of pregnancy, which function is not implemented through pharmacological, immunological, genetic or metabolic effects on the human body(No 323-FZ).

13. Registration of insulated shipping containers • Insulated shipping containers are used for the filling and transportation of temperature-sensitive drug products with the use of combination of frozen and/or cooled gel packs. • The requirement for the registration of insulated shipping containers as medical devices in the RF is redundant.

14. Packaging of insulated shipping containers Insulated shipping containers with gel packs and thermal loggers/indicators for temperature control used throughout the whole transportation route Certain type of filling of an insulated shipping container in certain packaging in regard to a certain temperature-sensitive DP must be validated by the distributor or manufacturer. Validation results must be formalized and routine filling operations must strictly follow the predefined filling layouts. There is a concern about the availability of resources, i.e. validation specialists and their competence...

15. List of typical GSP non-conformities • No detailed instructions on the actions of personnel in a warehouse with temperature-sensitive products in case of emergency (supplementary power supply, availability of a vacant prepared cold-storage vehicle, etc.). • Absence of the inventory of raw materials, materials and finished products stored at certain distributors/manufacturers with designated storage conditions. • Storage of rejected, recalled and returned products in non-isolated areas. • Refrigerators and freezers are unidentified, there are no labels with qualification status.

16. List of typical GSP non-conformities • No thermal mapping in warehouse for the detection of critical areas. • Areas, which should not be used according to the results of thermal mapping, are unidentified. • Location of temperature and humidity sensors are selected independently of thermal mapping results. • Products are placed between the storage racks, which does not coincide with the location of products during thermal mapping. • Internal surfaces of warehouse walls are not smooth, they are damaged, are hardly accessible for cleaning. • Time and temperature of leaving temperature-sensitive drug products outside storage conditions set in the ND are not defined. • Incorrect placement of ice pack/ wrongful preparation of gel packs for the filling of insulated shipping containers

17. Thank you for your attention! Questions? Quality Director, R-Pharm GC T.M. Vyazmina tm.vyazmina@rpharm.ru