Dr Raphael Bar, BR Consulting, Israel
Dr Torsten Sokoliess, Boehringer Ingelheim, Germany
This Education Course will give a comprehensive overview of tools that a Qualified Person (QP), Quality Assurance personnel or a Product Manager/ Manufacturer should have in order to evaluate the impact of excursions from the storage label instructions on the disposition of distributed shipments of pharmaceutical/ biopharmaceutical products.
The formal stability studies of pharmaceuticals and biopharmaceuticals are a well established discipline and they are regularly conducted at precisely monitored conditions of temperature (within 2°C) and of humidity (within 5% RH) under cGMP. However, the inevitable processes of shipping and distributing medicines from the manufacturer to wholesaler to warehouses to the end user via air, ship or car exposes often the shipments to temperatures and humidity different from the label storage conditions. For instance, how would you handle a shipment that was exposed to a varying temperature up to 61°C in the airport for an accumulated duration of several days? How would you evaluate the quality of a refrigerated injectable that was exposed to near zero or freezing temperatures for a few hours? Would you release or reject such a shipment which may cost hundreds of thousands of dollars?
Shipping/Distribution of a medicine is considered a “mobile storage”. However, a temperature excursion outside the label instructions may also be considered a ‘trauma” inflicted on the medicine and this may impact the quality of the newly arrived shipments. But, the big question remains: how would that ‘trauma” affect the quality at the end of the declared shelf life of any pharmaceutical and of a biopharmaceutical in particular? Will the long-term impact lead to a “hidden OOS”?
This course will address these aspects. Finally, a workshop will demonstrate how the evaluation of an example of a temperature excursion may be approached.
This Education Course will be of significant value to
- Qualified Persons
- Quality Assurance personnel
- Project coordinators/Product Managers
- Stability testing personnel
- Stability program logistics personnel
- R&D personnel involved in product development
Overview of Stability Programs and Stress Testing–Regulatory View (GMP and GDP)
- Long-term and accelerated storage conditions of new drug substances and products (EU, USA)
- Stability storage programs for generic drugs (EU, USA)
- GDP Guides (EU, WHO, USP Chapter <1079> )
- PDA Technical reports on GDP
Stress Studies of Pharmaceuticals
- Stressing factors and conditions
- Stress studies in the pharmaceutical industry
Degradation Rates of Pharmaceuticals
- Arrhenius kinetics
- Estimating degradation rate in a given temperature Mean Kinetic Temperature (MKT) and World Climatic Zones
- Mean Kinetic Temperature (MKT) and relative humidity
- Interpretation of MKT
- MKT from temperature loggers
Overview of Qualification of Shipment of Pharmaceuticals and Temperature Monitoring
ƒ The four Qs: DQ, IQ, OQ and PQ
ƒ Field studies and in controlled rooms
Evaluation of a Temperature Excursion in a Shipped Refrigerated Drug Product.
Storage Label Statements (EU and USA)
- Linking storage instructions to formal stability studies
- Labeling statements for various pharmaceuticals (EMA guideline)
- USP controlled temperatures
Shipping of Vaccines
- Various shipping conditions for vaccines
- Impact of temperature excursions on vaccines
- Vaccine vial monitor (VVM)
Stability Studies to Support Shipping/Distribution of Pharmaceuticals and Biopharmaceuticals
- Stress testing vs Forced Degradations
- Studies at elevated extreme temperatures
- Studies at low extreme conditions
- When, how and what?
- Thermal Cyclic studies
- What attributes to test
Design of Stability Studies to Support Shipping and Distribution of a Refrigerated
Protein Solution of a Biopharmaceutical Product.
Investigation of Excursions from Storage Label Conditions
- “Time-out-of-Storage” and stability budget“concept
- Handling an excursion
- What stability data are required to investigate temperature excursions
- Responsibilities of manufacturer, distributor and QP
Evaluation of a Temperature Excursion
- Estimation of degradation rates at the excursion temperature
- Estimation of degradation at the expected long-term shelf-life
- Estimation of a maximal “Time-out-of-Storage” of a drug