Batch manufacturing has been the traditional mode of manufacturing in the pharmaceutical industry for more than a generation now, but times are changing and more and more Contract Manufacturing Organizations (CMOs) are embracing continuous, or flexible manufacturing alternatives. But as with most things, there is a time and a place for everything, and while continuous manufacturing is growing in importance, it’s not time to send batch processing packing quite yet.
This article provides some insights into continuous vs. batch manufacturing.
With batch technology, the ultimate finished product is developed in a series of steps, which must be completed before a new batch can be processed. Using this method, CMOs can produce specific amounts of a certain product and then adjust their manufacturing priorities according to the changing demands of the market.
A benefit of batch production is that the set-up costs are typically modest, and each batch is more easily tailored to be unique. There are also certain drugs that can only be manufactured in batches because of their composition.
The pharmaceutical industry is filled with a variety of drugs under development with limited or unknown likelihood of clinical and commercial success. For products like these, it’s unrealistic for companies to take a gamble on the huge investment (upwards of $4-5M) that continuous manufacturing requires.
With batch processing, there also may be more flexibility if a company needed additional capacity. Because a continuous production line is designed specifically to process one specific drug, it may not be possible, in a shortage, to switch processing easily to another drug that requires a different process.
So, batch processing will continue to serve a need in the marketplace for the foreseeable future. The cost of building special GMP suites dedicated to the manufacture of a specific drug is unrealistic for most firms, unless it’s a blockbuster drug that requires continuous and fast production, and which will continue to have huge demand in the market.
Yet, continuous manufacturing is increasingly meeting a new need in the marketplace. It takes a drug from raw materials to final product – seamlessly – with no need to shut down equipment or have any down time as the product is created. The holy grail of continuous manufacturing would take all the ingredients in a single production line at one end, and the finished pill would come out the other. This is in contrast to combining ingredients processed by different partners and shipping to a finish dosage manufacturer. Continuous manufacturing, which is GMP compliant, requires a smaller physical footprint, which also helps it be a more environmentally friendly option.
The risk of human error is also reduced because continuous processing means fewer people are involved in the production process from start to finish. Additionally, the U.S. Food and Drug Administration (FDA) estimates that some drugs which normally take a month to produce using conventional batch processing, may only take one day to make using continuous manufacturing. This flexibility enables product to be produced in response to market demand (just-in-time) rather than the sponsor having to maintain large inventories in case of demand surges.
Another key benefit is that continuous manufacturing does not compromise quality – on the contrary, by eliminating breaks between steps and reducing opportunities for human error, many consider it to be more reliable — and safer.
Fast-tracked drugs. Many new therapies are receiving fast track, or Breakthrough Drug status, which allows them to take a much shorter clinical development path to FDA approval. While this is a good thing for the market and sponsoring firms, CMOs are challenged with significantly speeding up the chemistry and manufacturing processes using traditional methods.
Personalized medicine. New drugs can be highly targeted and potent, so the amount needed is often much smaller than traditional ones. The high price and novelty of these treatments can make it difficult to predict market demand and the amount to manufacture.
FDA guidance. Last year, the FDA came out with guidance to support flexible approaches in the manufacturing of quality pharmaceutical products. Entitled, “Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base.” The guidance encourages the development of emerging technology which may lead to pharmaceutical innovation and modernization, such as “a more robust drug product design and improved manufacturing with better process control, thereby leading to improved product quality and availability throughout a product’s lifecycle.”
The need for flexibility in manufacturing technologies has never been greater. New drugs can be more precise and powerful, produced in smaller volumes, and subject to great market uncertainty. While continuous manufacturing will increasingly play a greater role in large-scale commercial manufacturing, for early-stage development, batch processing will continue to be the de facto manufacturing process at least for the short term. The key is for manufacturers to explore all processes and be open to new technology innovations but take a realistic approach to ensure the most effective, practical and cost-effective route to pharmaceutical manufacturing.
For more information on continuous manufacturing check out:
https://www.manufacturingchemist.com/news/article_page/Initiating_change_in_drug_development_and_manufacture/108346 and http://www.pharmacompliancemonitor.com/the-future-of-facilities/8713/.