Continuous manufacturing: What is/isn’t happening and why 29th August 2018
By Emil W Ciurczak, President of Doramaxx Consulting
Emil W Ciurczak, President of Doramaxx Consulting, discusses the trends and opportunities for continuous manufacturing in th
A number of years ago, while I was a high school science teacher (a mere four years, but worthwhile) I was addressing some young people at a science fair. I did not go with a set agenda but wanted to field questions about science. One youngster asked about robots and when they will be coming (remember, this was 20+ years ago). I outlined what a robot did, in simplest terms: it 1) performs a simple operation, over and over, 2) without constant intervention, and 3) needs occasional calibration. When I asked what would qualify, only one young lady stated, “a clock.” Indeed, she nailed it.
- We’ve never done this, or we have no one with experience on staff
- We have so much money invested in traditional equipment, so why spend more?
- We can’t get it past Quality Assurance (QA) – a cry against ANYTHING different
- We have no place to set it up, and most common excuse
- We’ve always done it this way (and, its twin, “we’ve never done it that way”).
If you squint your eyes and look through a pair of reversed binoculars, you can see these arguments applied to the ‘large’ commercial tablet presses in the 1940s, assembly lines for cars in 1905, interchangeable parts for airliners in 1920, and almost any innovation over the last 150 years. In truth, these people tend to defer to ‘common knowledge’ such as, “A train can never go above 40 mph (67 kph) because people couldn’t breathe at that speed”, rather than try to prove whether something will or won’t work.
- The original compendial tests assumed that:
- All APIs were synthesized in-house or purchased from domestic sources, both under FDA (or EMEA) surveillance
- Excipients were obtained domestically from sources that were under FDA or (EMEA) supervision
- Suppliers were meticulous and “tests” were merely to assure the correct grade of material.
- The supply chain was far different then, but has changed in several ways:
- A typical Pharma company will purchase most, if not all APIs from third-party suppliers, often in different countries
- Excipients are also purchased, if not directly from other countries, then from distributers who, in turn, purchase from multiple countries
- Many larger Pharma houses (and generics) produce products in other countries where they source their own APIs and excipients; seldom
can any Agency find all the sources without some difficulty.
- To assure the grades and purity of APIs and excipients: ID, polymorphic forms, particle sizes, residual solvents, crystallinity, etc
- To check each step
- To use the monitoring data from each step to (eventually) control that step, assuring each point of the process was in control
- Assure both quality and consistency throughout each process and from batch to batch.
- Scale-up is unnecessary, since development scale-batches are the same as production-scale batches (which are just run longer)
- Clean-up is simplified
- Development (DoE) is faster and cheaper, since smaller lots are made and as many as 30-40 batches can be generated (and simultaneously analysed) in a few days versus weeks for “traditional” sized lots
- And, most importantly, lot #1 will be the same as lot #1,000,001.