A medicine production factory in Gujarat, India, almost halfway across the globe, was the origin of a scarcity of a crucial cancer therapy that has caused patients and medical professionals in the United States to scramble for other treatment choices.
In December, the Food and Medicine Administration began an inquiry into Intas Pharmaceuticals about the company’s manufacture of cisplatin. As a result of the investigation, the company decided to cease production of the medicine due to concerns regarding the product’s quality. Cisplatin is a medicine that is used to treat malignancies of the bladder, brain, throat, cervix, lung, ovaries, and testicles. By the month of February, the drug had gone into scarcity, and other suppliers were unable to fill the void left by the business that provides about half of the cisplatin that is used in the United States.
The Food and Medicine Administration (FDA) said in June that it would provisionally consent to the importation of medicine from China. The change will provide some relief, but it will not be a permanent solution.
The first step is to mine the raw material.
South Africa and Russia are the locations in question.
Platinum, which is needed in the production of cisplatin, must first be mined before it can be administered to cancer patients as a treatment.
According to Stephen Schondelmeyer, the director of the PRIME Institute, which conducts research on a variety of problems relating to pharmaceuticals, platinum is a very effective medicine, and in some preparations, it may be used to slow down or halt the growth of cancer cells. There are really three different types of chemotherapy drugs that are based on platinum: cisplatin, carboplatin, and oxaliplatin.
Platinum is a precious metal that can only be mined in a limited number of nations, namely South Africa and Russia.
According to Frank Gupton, the department chair of chemical and life science engineering at Virginia-Common-wealth University, this raises a number of potential concerns. These include supply vulnerabilities in the event that disruptions in mining take place, as well as potentially high prices due to the fact that the resource is controlled by only a select group of countries.
He said, “There is a general difficulty with getting this material since it is all made abroad.” This presents a problem when trying to obtain the substance.
After being extracted from the earth as an ore initially, the metal is then refined to get rid of any remaining impurities.
According to Matt Christian, director of supply chain insights at United States Pharmacopeia (USP), the process of refining platinum needs a specialized facility. This is because prolonged contact with the metal and the compounds used to refine it may be harmful.
The second step is the production of the API.
India and Germany are the locations in question.
According to Christian, once the platinum has been purified, it is sent to a manufacturing facility, where it is subjected to a chemical transformation in order to become cisplatin, which is the active pharmaceutical ingredient (API).
The active pharmaceutical ingredient (API) of medicine is the component of the drug that is accountable for the drug’s intended impact; in the instance of cisplatin, this effect is the destruction of cancer cells. (Another example would be semaglutide, which is the active pharmaceutical ingredient in the well-known drugs Ozempic and Wegovy.)
Active pharmaceutical ingredient (API) medications may also include additional components, such as preservatives or colors, which serve the purpose of maintaining the medication’s consistency and making it more visible.
The USP Medicine Supply Map has located API manufacturing facilities for cisplatin that are FDA-approved in Germany and India. The organization does emphasize, however, that it has not conducted an exhaustive review of every cisplatin plant in the globe.
According to Gupton, the transformation of platinum into cisplatin is a complex process. It requires the synthesis of the metal with two additional chemicals, ammonia, and chlorine, all of which are hazardous to deal with.
According to Gupton, in the same way, that they must be cautious not to expose themselves to the compounds during the creation of any medicine, the employees must also make sure that they do not contaminate the compounds.
He said that the issue you have is that anytime you handle these materials in an open environment, you may produce dust particles that are very difficult to manage. “The difficulty you have is that whenever you handle these materials in an open environment, you can generate dust particles.”
The procedure is very controlled, and the FDA has the authority to shut down a facility if it has reason to believe that there are contamination problems there.
According to Valerie Jensen, the assistant director of the medicine shortage program at the FDA, “the majority of our shortages are due to a production stoppage or a quality problem.” This may refer to anything that occurred during the manufacturing process or something that is at the site.
Step 3: Add the finishing touches
Locations include the United States of America, Germany, Italy, and India. The Netherlands.
According to Christian, the last phase in the process is known as “fill finish,” and it entails packing, labeling, and preparing the medicine for distribution. This step takes place after the creation of the active component.
According to the USP Medicine Supply Map, the production of cisplatin takes place at facilities that are FDA-approved in the countries of Germany, Italy, India, the Netherlands, and the United States.
According to Gupton, the medicine is initially sealed after it has been placed in its container, which might be a vial, a syringe, or a cartridge. He also said that this phase often takes place under carefully controlled settings in order to avoid contamination. After that, an inspection of the product to look for any flaws and the application of a label follow.
According to Gupton, the fill-finish plant may also be responsible for the distribution of the medicine, or it may be delivered to a distribution center.
He said that the majority had quite intricate distribution methods. “There is basically one degree of intricacy after another,” said the speaker.
“a fairly major obstacle,” in other words.
According to Erin Fox, an expert on supply chains and the senior pharmacy director at the University of Utah, Intas Pharmaceuticals in India ran into issues with the FDA during these final two stages – API manufacture and fill finish — which caused the company to be under pressure to cease production in the previous year.
According to Fox, “They had some quality flaws that they needed to correct, and they were not small.” In addition to this, it seemed as if personnel at Intas were attempting to hide the issues. According to the report from the FDA, before the inspection, the corporation used acid to destroy papers that pertained to the sterility and quality of the items. In addition to this, the agency criticized the firm for having ineffective cleaning procedures and for failing to take any precautions to avoid microbiological contamination.
Intas did not provide a response when asked for a statement.
However, since Intas was unable to continue operations, the FDA was unable to quickly transition to another manufacturer or locate an existing one that was prepared to increase output.
According to Fox, the cost of one dosage of cisplatin is around $16. The medicine is not very costly. The production of the API, on the other hand, is not only time-consuming but also costly. According to her, the poor profitability of the venture implies that very few pharmaceutical companies are prepared to pursue it.
She expressed her opinion that it is not “worth it for them to go to all the hassle of making.”
It is not possible for another medication manufacturer to immediately begin manufacturing the medicine, even if they are willing to do so.
According to Gupton, the manufacturing of pharmaceuticals such as cisplatin is a “very major difficulty.” “They are very controlled and extremely scrutinized, and there are a great number of locations that are unable to satisfy the requirements.”
According to what Schondelmeyer had to say, “It probably takes two years at least from the time that we realize we need a medicine to acquire FDA permission and get a facility up and running and get manufacturing started again.”
This dilemma demonstrates how even a single bottleneck in the supply chain has the potential to prevent patients from receiving required therapy.
According to what Schondelmeyer had to say about the situation, “It’s a problem of public health and a question of national security.”
In May, Michael Thompson, 60 years old and from Iowa, was given a diagnosis of stage 3 throat cancer. Two months later, in July, he found out that he would be administered carboplatin rather than cisplatin due to the persistent lack of cisplatin. This news came as a disappointment to him. Although the two medications are comparable in that they are both based on platinum, his physicians have informed him that carboplatin is a less effective treatment for his disease. (According to the FDA, carboplatin, which is also manufactured by Intas, is likewise in low supply.)
The words of Thompson ring true here: “You can’t prepare yourself for that type of news.” “The fight against cancer is complicated enough on its own. But then, dude, you don’t want to be faced with the news that the therapies that you need aren’t accessible because that is really difficult to swallow. “But then, man, you don’t want to be hit with the news that the treatments that you need aren’t available.
The FDA has said that it is taking all necessary steps to remedy the issue.
In June, the government agency said that it would import cisplatin with the help of a Chinese pharmaceutical manufacturer called Qilu Pharmaceutical. Although the FDA in the United States has not given its approval for the use of the cisplatin developed by Qilu, it is sold and manufactured in China. The import plan is projected to expand the availability of chemotherapy medicine in the United States.
The FDA’s Jensen referred to this solution as a “temporary fix.” This import will continue as long as the permitted producers are unable to satisfy the requirements of all of the patients.
Jensen also said that the FDA is speeding up its consideration of everything that another firm could need in order to begin producing cisplatin or increase its current production capacity. In addition, the government has decided to grant Intas Pharmaceuticals permission to sell in the United States certain cancer medications that are currently unavailable, such as cisplatin. However, before the items can be disseminated, a third party will need to certify the products’ quality, as stated in the paper that was provided by the agency.
Fox said that the measures made by the FDA are suitable but noted that they do not fix the significant problems with the supply chain.
“There are a lot of unknowns right now, and clinicians are simply extremely cautious about creating plans for patients because of this,” she added.
In the meanwhile, Thompson is keeping his fingers crossed that the therapy he does end up getting will be successful. If it doesn’t work, his doctors are recommending a complete laryngectomy, which is surgery to remove his larynx entirely. After that, he wouldn’t be able to talk anymore.
According to what he had to say, “It’s an emotional fight because you know you’re facing a battle for life and death.” answer or remedy.
The disruption that occurred in India demonstrates how a single bottleneck in the production process of medicine may throw the whole supply chain into chaos. However, hospitals in the United States do not just import cisplatin from India. This is not the case for many other medications that are used locally and internationally. In the course of its production, the medicine will make a number of stops, one of which will be in India.
News mapped the global journey of cisplatin with the assistance of the United States Pharmacopeia Medicine Supply Map, a database that offers insights into the international drug supply chain. The trip was mapped from the mines where a key component is extracted from the earth to the distribution centers where it can be sent on its way to reach patients who are in need of it.