Eli Lilly develops continuous manufacturing process for chemotherapy drug

June 16, 2017 by Bob Yirka report
Photograph of deprotection gas/liquid reactor during processing. Credit: Eli Lilly and Company.

Researchers at pharmaceutical giant Eli Lilly have developed a continuous manufacturing process for a chemotherapy drug, officials with the company recently announced. In their paper published in the journal Science, the research team describes the process, how it works and possibilities for further projects.

Making legal drugs is big business, and huge pharmaceutical companies such as Eli Lilly have invested a lot of money in streamlining the process. Most drugs are made on a mammoth scale in step-wise processes designed to produce the largest amount possible of a drug at the lowest cost. But sometimes, that approach is not optimal—such as when a company wishes to conduct a clinical trial to test a new drug. In such a scenario, huge amounts of drugs are not involved which means drug companies face a tough choice: produce much more of the drug than is needed in a traditional production facility or make it in a small lab by hand. Both options are very costly. For this reason, have been looking at a new way to produce drugs called continuous manufacturing. In this approach, drugs are made in a continuous process rather than as a series of steps. Creating such processes has proved to be challenging, however, because making drugs is not just a matter of mixing ingredients in a tub. It involves inducing chemical reactions, for example, or growing crystals. In this new effort, the researchers at Eli Lilly report a technique to make small amounts of prexasertib monolactate monohydrate—a drug to be tested in a clinical trial for use as part of chemotherapy for cancer patients.

To be useful, a continuous manufacturing process must meet what are known as Good Manufacturing Practices, in which important parts of the process can be monitored by quality control systems. In the case of the new system, the research team chose prexasertib specifically because it is challenging to make—one of the parts of the process involves using hydrazine, an ingredient in rocket fuel. Also, the finished product is toxic, which presents problems for workers trying to make it.

The researchers report that the system is able to produce 3 kg of the per day, enough for use in their proposed . They also report that moderate human intervention is required to keep the system running.

Explore further: Predictive model helps identify drugs currently in use that could be used to treat other ailments

More information: Science  16 Jun 2017: Vol. 356, Issue 6343, pp. 1144-1150. DOI: 10.1126/science.aan0745 , http://science.sciencemag.org/content/356/6343/1144

Abstract
Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound.

Related Stories

Predictive model helps identify drugs currently in use that could be used to treat other ailments

March 30, 2017
(Medical Xpress)—A team of researchers from several institutions in the U.K. and one in the U.S. has developed a faster and cheaper way to figure out which drugs on the market might be useful for treating other ailments. ...

Pharmacy on demand: New, portable system can be configured to produce different drugs

March 31, 2016
MIT researchers have developed a compact, portable pharmaceutical manufacturing system that can be reconfigured to produce a variety of drugs on demand.

Lilly's rheumatoid arthritis pill rejected by regulators

April 14, 2017
Eli Lilly said U.S. regulators have rejected its much-anticipated pill for the immune disorder rheumatoid arthritis, the drugmaker's second drug development setback since November.

New model can predict drug interactions and side effects even between a large number of components

April 10, 2017
Drug cocktails such as those for treating cancer, like the alcoholic versions offered at the local bar, are best when the proper ingredients are mixed in the right proportions. And like the cocktails we normally drink, the ...

Recommended for you

Data revealed under FOI shows benefits of multiple sclerosis drug currently blocked by regulators

August 17, 2017
A drug that is blocked by the EU regulatory system has now been found to improve the quality of life of people with multiple sclerosis (MS), according to a study by Queen Mary University of London (QMUL).

Opioids overused in migraine treatment, regardless of race, study finds

August 17, 2017
African-Americans are more likely to experience debilitating migraine headaches than whites, but a new study probing the issue found no evidence of racial disparities in treatment practices.

Finding better ways to reduce serious drug side effects

August 14, 2017
Many of the medicines we depend on to treat disease—and even to save our lives—pose potentially serious risks along with their benefits. Data from the U.S. Centers for Disease Control and Prevention indicate that about ...

Ultrasound-triggered liposomes for on-demand, local anesthesia

August 10, 2017
Researchers at Boston Children's Hospital have found a new way to non-invasively relieve pain at local sites in the body; such systems could one day improve pain management by replacing addictive opioids and short-lasting ...

Independent pharmacies and online coupons help patients save money on drugs

August 8, 2017
Uninsured patients or those with limited prescription drug coverage can save significant money by buying their drugs at independent pharmacies instead of big box, grocery or chain drug stores and by using discount coupons, ...

New study generates more accurate estimates of state opioid and heroin fatalities

August 7, 2017
Although opioid and heroin deaths have been rising dramatically in the U.S., the magnitude of the epidemic varies from state to state, as does the relative proportion of opioid vs heroin poisonings. Further complicating the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.