Causes of supply bottlenecks for medicines
Pharmaceuticals are an important part of medical care. The importance of this becomes particularly clear when, of all things, the drug that is to be used is not available. In their own interest, manufacturers work hard to ensure that they are always able to deliver. And if delivery problems do occur, they strive to overcome them as quickly as possible. However, as with other technically manufactured products, it is impossible to rule out the possibility that a drug may temporarily not be available in the quantities required.
Delivery problems are associated with lost sales for manufacturers and also reduced market opportunities in the future. Therefore, all manufacturers strive to avoid supply bottlenecks through reliable production facilities, demand estimates and stockpiling.
Fortunately, only individual package sizes or dosage forms are usually in short supply; it is then usually possible to switch to other packages or dosage forms. In the case of off-patent drugs, it is usually possible to switch to another supplier.
New strategy needed for pharmaceutical supply chains
- Pharmaceutical supply chains are robust
- 68 percent of production sites are in China and India
- Strengthening high-tech in Germany is important
- Possible solutions
Causes of supply shortages
The causes of supply shortages are different in each case. Sometimes ...
- a drug is bought up by parallel exporters from the German trade and transferred to the distribution of another EU country because the German price has been lowered below the price there and, moreover, is publicly available to any distributor,
- a supplier has delivered the active ingredient or another basic ingredient too late;
- production comes to a standstill due to a shortage of an excipient or packaging material, although enough active ingredient is in stock;
- there are production problems due to a major machine malfunction;
- a plant has to be temporarily shut down for expansion, conversion or repair work - or production is relocated and the stock built up to bridge the gap is insufficient due to unforeseeable delays;
- a production batch cannot be released for distribution due to defects or has to be recalled because of this. Post-production takes time;
- demand increases unexpectedly (e.g. due to a wave of illness or because another manufacturer has dropped out) and production cannot be ramped up as quickly;
- new legal regulations also lead to restrictions, e.g. if they require changes in production or there are delays in approving such changes.
In the case of vaccines, there is also the fact that their production is complex and costly. It is not uncommon for delays to occur in the production process for individual vaccine components, as problems can repeatedly arise in the multiplication of the required pathogens. The production of a combination vaccine takes about 12 to 26 months and is accompanied by hundreds of in-process controls and release tests to ensure the quality and safety of the final product.
For influenza vaccines in particular, no stockpiling is possible: these are shipped immediately after completion and regulatory approval in the fall. This is because new flu vaccines are needed every year to match the ever-changing influenza virus strains. Since the production process must be adapted to the changed virus strains in a time-intensive manner, production cannot begin immediately after the seasonally relevant virus strains have been determined by the regulatory authority. There are also sometimes problems with the propagation of individual virus strains. All this can lead to individual or all manufacturers not being able to deliver the planned quantities on time.
Only the respective manufacturer itself can provide information on the causes of specific delivery problems or recalls of individual drugs.
Because the causes of supply bottlenecks are different in each case, there is no standard measure that can be used to overcome them all. Individual solutions are required in each case, which must be coordinated with the approval authority. For example, a manufacturer who has repeatedly been unable to obtain supplies from one supplier will seek out other sources. Before goods from this new supplier can be used, however, extensive quality assurance is necessary.
Measures against supply bottlenecks
Supply security depends on functioning supply chains. To strengthen these, a combination of different measures is needed. At their heart is a global distribution of the production needed for a drug in order to reduce individual dependencies within pharmaceutical supply chains. Europe's high dependence on Asian active ingredient manufacturers is problematic. There are 68 percent of the production sites of certain active ingredients for Europe in Asia. Fast approval procedures, better access to venture capital and internationally competitive tax rates for innovative pharmaceutical companies could make Germany a more attractive location again. In addition to this, the data infrastructure must be significantly improved (digitization).
Fortunately, a manufacturer's supply problems often do not result in supply problems for patients because other manufacturers of drugs with the same or similar active ingredients can close the gap with their supplies.
Supply shortages for supply-relevant drugs are reported by the marketing authorization holders to the Federal Institute for Drugs and Medical Devices (BfArM) and published on its website. In addition, the BfArM provides more detailed information on specific supply bottlenecks in individual cases and presents measures to ensure that as many patients as possible can be supplied with the drug in question.
This does not apply to vaccines that are currently not available. For this purpose, the Paul Ehrlich Institute (PEI), as the responsible drug authority, provides information on its website about which vaccines can be used instead of the unavailable one.
A list published by the German regulatory authorities since the end of April 2013 entitled "Supply bottlenecks of human medicines" is also helpful. This contains notifications from manufacturers of supply shortages, particularly of those medicines intended for the treatment of life-threatening or serious diseases, and for which no alternative preparations are available. This constantly updated overview is helpful for users (e.g. hospitals), who can thus better prepare for announced shortages. It can also help other manufacturers to increase their production in good time.
However, it is not possible for other manufacturers to arbitrarily increase their output "on demand", even if this means they lose sales opportunities. After all, it often takes months from the first production step to the finished drug. This is particularly true for vaccines, genetically engineered products and cytostatics for cancer medicine. Also, in some cases, chronically ill patients cannot easily switch their long-term treatment to a similar drug from another manufacturer without risking adaptation difficulties with regard to efficacy and side effects; this applies, for example, to insulin preparations.
Healthcare stakeholders consulted
Starting in the fall of 2016, meetings were agreed upon between representatives of the Federal Ministry of Health, the drug authorities BfArM and PEI, the medical societies, the drug commissions of the medical profession and pharmacists, pharmacists and wholesalers, and four pharmaceutical associations. In July 2020, the previous Jour Fixe on supply and supply shortages was transferred to the Advisory Board. Its purpose is to monitor and evaluate the supply situation. As a further result, the pharmaceutical industry has undertaken to contribute to an improvement in the supply situation by further optimizing its processes and quality management.