Fill & Finish of the Future
The technology has barely changed over the last 30 years – surely, it’s time for some long overdue innovation.
Susan Dexter |
When it comes to the final stage of packaging before a product is injected into the patient, it’s understandable that the regulators expect perfection, both in process and the related documentation. This is the last line of defense. Over the past five years, there have been a significant number of quality and compliance issues identified by the FDA, particularly in documentation and quality control. The ‘checks and balances’ that prove sterility are fallible. Indeed, every vial can’t be checked for sterility, so it’s vital to have several layers of accumulated data to be confident that the product is safe. If there are chinks in the armor of quality systems – even if the sterility testing identified no issues – the FDA will not feel confident in the product.
So how can new technology make life easier for manufacturers and regulators alike? By making compliance simpler. For example, automated systems reduce the risk of protocol violation, while barrier technology and disposable elements remove the risk of cross-contamination. Forward-looking companies are already implementing these measures in their plants.
Such advances will make a big difference to quality and efficiency of fill/finish. But I want to look beyond that, to the truly disruptive technology that will transform the industry and give the process a whole new level of protection. For example, in a recent panel session at INTERPHEX 2015, MedInstill presented their “Closed Intact Transfer” technology, their vision of the future for fill/finish. This is a fully automated system, 21 CFR 211 compliant within a controlled non-classified environment. The fill step is conducted in a sterile environment between a pre-sterilized closed filling needle and a pre-sterilized closed container. The needle is “decontaminated by friction force” (FDA definition) as it pierces the container septum, creating the barrier system equivalent. The needle opens within the container, fills and re-closes still within the container, and then withdraws. The self-reclosing septum of the container is then terminally resealed with laser or hot-melt. In comparison, traditional filling is conducted into open containers, which get capped afterwards. This necessitates operating in controlled classified environments with multiple in–out transfers for the containers, caps, filling cannula and personnel during intervention. These are a lot of moving parts and a lot of opportunities for non-compliance.
The results of the new process so far look impressive. Of course, it’s never easy implementing disruptive technologies. There will be a great deal of education involved, for both manufacturers and regulators. Companies will need to show the FDA and other regulators why and how the new technology will reduce risks to patients. The regulators want better products for the public and are open-minded to new technology – but they will also have a lot of questions to ask. Several pioneering companies will have to go through the process with them, and face the risk of delaying their entry to the market. In extreme cases those delays could have a huge impact on the profitability of the drug, so it can be a double-edged sword. However, this is the case with all major innovations in pharma, and if the technology is good enough, someone will step forward and take on that risk.
It’s been a long time coming but the mindset of people in the industry is shifting to focus on the possibilities rather than the pitfalls. To date, fill/finish has been taking incremental baby steps, but I believe the time has come for the industry to start making bigger leaps forward.