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Elham Blouet from Roquette explains the importance of carbohydrates for injection and the challenges in this niche market.
How important are carbohydrates for injectable use in Europe?
When manufacturing large-volume parenteral preparations, such as parenteral nutrition or dialysis preparations, as well as injection preparations used solely as nutrient or as a vehicle for ethical drugs (medicinal products delivered under prescription), carbohydrates are essential. Carbohydrates, such as glucose, are the main source of energy for body cells. Although most body cells can utilise fats for energy in a pinch, brain cells and red blood cells rely almost completely on glucose to fulfil their energy needs. Glucose, the main type of carbohydrates used in parenteral preparations, is considered a life-saving molecule because it is used as first-line treatment in emergency situations that lead to dehydration and acute hypoglycaemia.
Manufacturing carbohydrates-based parenteral preparations requires highly controlled APIs. Parenteral preparations are sterile drug products and their manufacturing conditions are subjected to strict requirements and standards, including a high level of microbial and physiochemical quality for raw materials APIs. Inferior quality of such APIs can jeopardise the entire parenteral drug, with a serious impact on patient safety.
Injectable solutions prepared with carbohydrates are used on a mass scale in hospitals and other healthcare settings, but are often taken for granted because they are expected to be available everywhere and at the highest quality. For manufacturers, however, these specialised ingredients are small scale compared with the wider portfolio of products and other applications from the starch biorefinery industry, such as food, feed nutrition, chemical and industrial applications. In addition, organic growth is limited; in Europe, access to healthcare is ensured for all the population regardless of social status or age. Even though the extension of life is obvious in Europe, the spread of access to healthcare counterbalance any substantial organic growth.
What are the main challenges associated with manufacturing carbohydrates for injection?
Health suppliers, hospitals and clinics regard carbohydrates for injection as commodities and, as such, they are a preferred target for price reductions, which makes it a challenging area for manufactures to invest in. In addition, manufacturers face continually evolving regulations and quality standards; for example, implementation of the ICH Q9 and Q11 guidelines and the recently adopted EC Directive on Falsified Medicinal Products (amending Directive 2001/83/EC) will require manufacturers to reinforce their existing quality management system even further. Finally, because carbohydrates for injectbale use are commonly processed from natural origin raw materials (such as cereals), their production requires sophisticated and well controlled processes and purification steps.
Considering the challenges in injectable carbohydrate manufacture, why did Roquette decide to invest in this niche market?
We have invested in this market by creating a new injectable carbohydrate facility in Lestrem (France). Such a niche market is a challenging environment for investment, but Roquette however, decided to proceed with the investment as part of its long term strategy to remain a responsible supplier in this demanding field. In fact, Roquette has pioneered the development of glucose grades for the preparation of injectable and dialysis solutions over many decades and is the leader in the manufacturing of such carbohydrates in Europe.
This leadership position comes with a sense of corporate responsibility to ensure the continuity of these vital products and this in turn has lead to continuous investment.
How are difficulties in the supply chain managed and accounted for to ensure an uninterrupted supply of these crucial medicines?
Supply chain continuity is a critical issue for carbohydrates for injectable use because of their criticality in healthcare settings. Any disruption in the supply chain could lead to shortages, which would endanger patients. Supply chain difficulties can be managed by implementing a solid business continuity plan; indeed, ensuring supply chain continuity should be a key part of such a plan. At our company, we use several production sites to help ensure production continuity. For example, our glucose production facility in the US can act as a back up to international supply.
It is also important to have reliable supply chain and distribution networks that ensure the traceability and the continuity of supply. Less players in supply chain, to some extent, equals less vulnerability, However, it is always important to verify that all supply-chain players have a quality management system in place to ensure traceability and action plans for the continuity of supply.
Do you think any further improvements can be made to the production of carbohydrate products for injection?
The production of carbohydrates product for injection is based on well-known technologies such as controlled hydrolysis and purification. Any further improvements could be driven by new sophisticated technologies in purification processes, for instance. In addition, processes may also be influenced by European regulations, which are constantly evolving.
With the new ICH Q11 related to the development and manufacture of drug substances, the "enhanced approach" compared with the "traditional approach", development must be based on risk management and more extensive scientific knowledge in order to select unit operations and process parameters that impact critical quality attributes for evaluation in further studies to establish control strategies. In the “traditional approach”, the set points and operating ranges for process parameters are defined and the control strategies are based on demonstration of reproducibility and compliance to acceptance criteria.
Will new or changing regulations in Europe have any affect on the manufacture of carbohydrate products?
Regulations in Europe are continuously evolving.The adoption of directive of Falsified Medicines was driven by the last events on drug medicinal products manufactured with falsified API’s which reached the market via the legal supply chain (example; heparin case). The aim is to strengthen the control of whole manufacture and distribution system of pharmaceutical ingredients and drug products according to GMP and GDP.
These regulations will affect to a certain extent the development and manufacture of active ingredients. For instance, development and manufacture of drug product based on risk-assessment approaches (ICH Q8, Q9) has been extended to API’s development and manufacture (ICH Q11): conception of quality is definitely connected to safety of patients.