Wie kent er beursgenoteerde bedrijfjes die toeleverancier zijn voor bedrijven als Moderna?
Why tech transfers are difficult
The safety, quality, and efficacy requirements of life-saving but potentially toxic pharmaceuticals put high demands on production. Producing complex pharmaceuticals is not just a matter of building the required production line or hardware. It also involves a complex (and often finicky) manufacturing process, a large team of experts, a lot of time, many detailed steps, and the right regulatory registrations—and all of this against the highest quality standards.
The production process for vaccines, as for any biopharmaceutical, can be hard to control for many reasons (Exhibit 1). The products are grown in live microorganisms or are parts of live microorganisms. The variability of biological processes needs careful calibration, validation, and constant tuning to ensure consistency.
This, in turn, requires a complicated dance of multiple experts in manufacturing, quality, regulation, engineering, and logistics—also, trainers, lab technicians, smart builders, maintenance crews, scientists, and capable leaders. An average transfer requires six to nine full-time equivalent hours (FTEs) from a dozen disciplines. If we have ten to 20 vaccine candidates with four to eight sites per candidate, we will need 300 to 1,200 specialist FTEs. Owing to the discipline split, this might amount to as many as 2,000 to 6,000 professionals.
Typically, the tech-transfer process is invisible to patients and even to many professionals in the industry. Clinical trials in pharma can take between five and eight years. Tech-transfer times for sterile dosage forms, such as injectable vaccines, range from 18 to more than 30 months (Exhibit 2). Because this timeline is shorter than the average clinical-trial length, pharmaceutical engineers can work carefully and diligently on the transfer process, knowing it is not on the critical path.
That will not be true for a COVID-19 vaccine or therapeutic. Society will demand the shortest possible timeline. Once a successful vaccine is confirmed, manufacturers will be under extreme pressure, and tech transfer will need to happen as soon as possible, within a few months.
The duration of a tech transfer is driven by eight main steps with eight functions at two sites, often also involving equipment and material suppliers. Each of the steps contains around 20 to 30 separate activities, so individual actions number in the hundreds. The wide variety of functions involved is spread across the donor site, the receiving site, and sometimes also a headquarters site (Exhibit 3).
In normal times, tech transfers can suffer from a lack of attention during routine production. They can receive little priority at donor sites and often are not top of mind at receiving sites. In the current situation, manufacturers are focused on delivering other essential vaccines or coping with the exceptional swings in production caused by lockdowns. Also, many smaller vaccine producers will be doing a tech transfer for the first time, which creates risk.
The transfer for new COVID-19 vaccines will likely involve a scale-up step, where equipment is used for the first time, placing high demand on process development and experts in manufacturing science and technology. And commercial transfers between sites often require equipment modifications and process adaptations, which add complexity.
Also, quality standards for vaccines are strict, since vaccines are administered to healthy people. Therefore, regulators require quality controls logged in a set of documents and submissions—chemistry, manufacturing, and controls (CMC)—which allow the regulators to manage whether manufacturers and developers are taking proper precautions. Creating the filing, registration, and underlying data is a labor-intensive process.