- Raw materials
- Process equipment
- Product quality
Thursday, October 13, 2011
Lately we have been reading and hearing shortages of many drugs. As a matter of fact the US FDA on a routine basis publishes the list of drugs that are in short supply. Families and doctors of patients who need these drugs have a cause of concern. Hospitals, where some of these drugs are needed, have become creative to determine what possible approved substitutes could be used. This can be a challenge. It would be worth reviewing the cause and cure of the 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 shortage. Regulations are minimal and might be a challenge who do not follow them and/or do not have equipment that is suited for the process. If the companies cannot follow these minimal standards then their being in the business should be a cause of 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.
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, review the effect and cause of the above four.
Since pharmaceuticals are highly regulated to protect patients, regulatory bodied particularly the US FDA proposed good manufacturing practices "cGMP". They have become the global benchmark. Some may consider them to be difficult to incorporate in their manufacturing routine but they are minimalist. Science and engineering curriculum teach us methods that if applied properly will exceed the "cGMP" guidelines and will cost less than any one 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 will cost additional money and there are no assurances that each subsequent pass will produce quality product.
Some of the steps to avoid shortages are well known. Occasional review helps.
To ensure raw material supply, developers have to qualify more than one supplier who can supply materials on a timely and as needed basis. In addition, the process developers have to make sure that the materials from each alternate supplier can be converted to 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, API/formulated drug volume per batch per plant are generally low compared to the volume of fine/specialty chemical products. Since the API/drugs due to their toxicity 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 requires a revamp of manufacturing and business strategies.
Product quality is dependent on process robustness. However, in pharmaceutical manufacturing especially in the manufacture of API, due to low dosage resulting in significantly low volume of API 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 the current methodologies and manufacturing set up engrained in our thinking the problems of shortages will persist. This can only be eliminated if we overhaul of the process development and manufacturing strategies. However, due to high profitability such a shift might not be in the offing.
Manufacturing technologies used in the pharmaceutical manufacturing are borrowed from the chemical industry. Chemical industry believes in 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 at formulation of drugs. Many might not agree but API manufacturing, heart of every drug, is generally not considered part of the pharmaceutical manufacturing. This adds to the problem.
Why and how manpower enters into the quadratic shortage equation as it should not? 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 i.e. potential product shortages. Constant manpower training can add to manufacturing delays and 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 in the same equipment. Re-training of manpower if needed would 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 to.
Girish Malhotra, PE