Lately, we have been reading and hearing about the shortages of many drugs. As a matter of fact, on a routine basis, the U.S. FDA publishes a list of drugs that are in short supply. Families and doctors of patients who need these drugs have a cause for concern. Hospitals, where some of these drugs are needed, have become creative in determining what possible approved substitutes could be used. This can be a challenge. It would be worth reviewing the causes and some cures for these shortages.
Before we begin to discuss the reasons for the shortages, I would like to clarify one point. We cannot and do not have any reason to blame any of the global regulatory bodies for these shortages. Regulations are minimal, and may be a challenge to those who do not follow them and/or do not have equipment that is suited for the process. If companies cannot follow these minimal standards, then their being in the pharmaceuticals business should be a cause for concern.
Since drugs are manufactured, the shortages can be created by any or combination of the following. There can be other reasons also, but I believe the following generally are the most important:
- Raw materials.
- Process equipment.
- Product quality.
The above individually and or collectively can and will cause product shortages in any business where products are manufactured and/or are assembled. The reasons outlined above are not new. Every business and engineering curriculum, where manufacturing processes are discussed, reviews the cause and effect of the above four.
Since pharmaceuticals are highly regulated to protect patients, regulatory bodies -- particularly the U.S. FDA -- propose good manufacturing practices or cGMPs. These have become the global benchmark. Some may consider them to be difficult to incorporate in their manufacturing routine, but they are really minimal.
Science and engineering curriculum teach us methods, which if applied properly, will exceed the cGMP guidelines and cost less than anyone can imagine. We just have to do the right things in the first pass. We all know that second or additional passes to achieve quality costs additional money, and there are no assurances that each subsequent pass will produce a quality product.
Some of the steps to avoid shortages are well-known, yet occasional review helps.
To ensure raw material supply, developers have to qualify more than one supplier who can supply materials on a timely and an as-needed basis. In addition, the process developers have to make sure that the materials from each alternate supplier can be converted to a quality product. Such an exercise can minimize availability and scheduling issues.
If the equipment used to produce a product is not designed for the process, product quality issues will come up.
Another cause of delays can be equipment availability. We need to recognize that due to low dosage, active pharmaceutical ingredient (API)/formulated drug volumes per batch per plant are generally low compared to the volume of fine/specialty chemical products.
Since API/drugs use their toxicity to cure a disease, it is necessary that the equipment be very clean to prevent cross-contamination. This, due to low-production volume, can result in equipment availability and scheduling challenges individually and/or collectively. All these can lead to product shortages. There are ways to eliminate these situations, and this requires a revamp of manufacturing and business strategies.
Product quality is dependent on process robustness. However, in pharmaceutical manufacturing, especially in the manufacture of APIs, due to low dosage resulting in significantly low volume of APIs per batch per plant, economies of scale, i.e. the best processes are not possible unless an effort is made to have designated equipment for the product. With current methodologies and manufacturing setup engrained in our thinking, the problems of shortages will persist. This can only be eliminated if we overhaul the process development and manufacturing strategies. However, due to high profitability, such a shift may not be in the offing.
Technologies used in pharmaceutical manufacturing are borrowed from the chemical industry. The chemical industry believes in the process of continuous improvement, Lean manufacturing, Six Sigma and quality first through competitive innovation. Pharma has not done so and needs to do that. There is significant discussion and all seems to be focused on the formulation of drugs. Many may not agree, but API manufacturing, the heart of every drug, is generally not considered part of pharmaceutical manufacturing. This adds to the problem.
Why and how manpower enters into this quadratic shortage equation is interesting as it should not. The reason it does is due to very infrequent runs of the same product. Since many different products are produced using the same equipment, there is constant juggling of materials and methods. All this can lead to errors and potential product shortages. Constant manpower training can add to manufacturing delays and a lack of it can cause off-quality product, resulting in shortages.
Companies need to consider and invent methods that will eliminate shortages. This could be higher production volume per run or better technologies, so that different products can be produced with the same equipment. Retraining of manpower, if needed, will be more organized.
One solution can not fit every product or company. Each company has to review its situation and has to take steps to minimize shortages. They can be minimized if we want them to be.