The FDA is implementing a new programme allowing pharma companies to submit novel manufacturing technologies for expedited review. Abi Millar asks how the process will work in practice.
For many pharmaceutical companies, traditional manufacturing technologies no longer seem up to scratch. Faced with increasing cost pressures, they are seeking ways to speed up operations and to do more for less. This may mean automating processes that were previously manual, or deploying equipment that enables higher production yields.
This isn’t just about cutting costs – through modernising their systems, they stand to improve product quality too. For instance, a number of drugs companies are starting to rely on single-use equipment, which reduces the risk of contamination and subsequent batch recalls. Often, this is integrated into continuous manufacturing processes, which leads to greater product consistency as well as lower operating expenses.
Here, there are clear ramifications for patient care. With almost two thirds of all drug shortages caused by manufacturing and quality issues, a small blip at the manufacturing plant can have devastating consequences further down the line. In this climate, emerging technologies are coming to seem increasingly attractive.
“Modernising manufacturing technology will lead to a more robust manufacturing process with fewer interruptions in production, fewer product failures – before or after distribution – and greater assurance that the drug products manufactured in any given period of time will provide the expected clinical performance for patients,” explains a spokesperson for the US FDA.
Unfortunately, in such a tightly regulated industry, it isn’t always easy to be inventive. Any new technology, whatever its benefits, will need to be carefully assessed by the regulators to see whether it meets existing guidelines. And while nobody would begrudge the need for compliance, reviewers may take a while to familiarise themselves with the new equipment, leading to delays.
A company may therefore find itself in quite a bind – stick with the old technology, and deal with a less than ideal manufacturing process, or adopt something more cutting-edge and face setbacks at the regulatory end. Neither is conducive to optimal drug development – getting the drugs as quickly and safely as possible to the patients who need them most.
Addressing the issues
In December 2015, the FDA acknowledged these issues, with the release of its draft document: “Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base Guidance for Industry.” This document discusses a new programme that will help companies integrate such technologies more quickly.
“In order to encourage more advancements in pharmaceutical manufacturing, FDA recognised the need for a new approach,” explains the spokesperson. “We established the Emerging Technology Team (ETT) to work directly with industry to help identify and resolve scientific issues for new technologies.”
The Emerging Technology Team, part of the FDA’s Center for Drug Evaluation and Research (CDER), will be the first port of call for pharma companies looking to implement a new manufacturing technology. The team will answer questions about the information FDA expects to see in a submission, helping to facilitate a speedy regulatory review.
“Pharmaceutical companies can have early discussions with the ETT regarding manufacturing design and development issues, as well as to obtain FDA’s recommendations for regulatory submission content related to new manufacturing technology,” continues the spokesperson. “When regulatory submissions involving novel manufacturing technology are received by FDA, the ETT will work collaboratively with the pharmaceutical quality review offices to ensure timely assessment of the submission.”
Speeding up the process
Together with the relevant CDER pharmaceutical quality offices, the team will assess the quality of any submission, helping determine whether or not it is approved. For the most part, the key issue is regulatory compliance – will this manufacturing technology both serve its intended purpose (improving product safety, strength, quality or purity) while sticking within the parameters of existing safety rules?
However, FDA policy has never been static, and in certain instances, a new technology may prompt an amendment to its wording. The ETT will therefore identify and capture any resolution to policy issues that may inform FDA approaches. It will also make recommendations regarding future submissions that involve the same technology, speeding up the process even further.
“The ETT’s involvement, all the way from the early technology development to application review, will help ensure the consistency, continuity and predictability in review and inspection of emerging technology,” says the FDA spokesperson. “Such early engagement enables the FDA to proactively identify and address potential roadblocks and helps eliminate potential delay in the adoption of promising new technologies.”
The next steps
This is not the first time the FDA has evinced its commitment to modernising manufacturing technologies. As early as 2002, the agency launched an initiative called ‘Pharmaceutial cGMPs for the 21st Century: A Risk-Based Approach” which aimed to bring the pharmaceutical quality assessment up to date. In 2004, it released further guidance detailing what ‘quality’ truly means: essentially that it cannot be tested into products, but should be present by design.
The release of this latest guidance, however, spells a step change for the pharma industry, removing the stumbling blocks that might discourage a manufacturer from trying something new. Having solicited feedback from interested parties, FDA plans to finalise the details of the programme later in the year.
For now, pharma companies are encouraged to express their interest by placing an electronic request to CDER-ETT@fda.hhs.gov. This specifically applies to drugmakers who wish to submit an investigational new drug, or an application for a new drug, generic drug or biotechnology product that includes temerging technology.
FDA has said it will notify companies of its decision within 60 days of receipt of the request. If that company is accepted into the programme, it will then be able to engage with the ETT review team and get the ball rolling towards approval. Of course, the process may still prove more complicated than adopting something tried and tested. But with the need for innovation more pressing than ever, a dedicated programme is sure to give manufacturers an extra incentive.
Hearteningly, FDA is not putting a cap on the number of participating manufacturers, but will aim to ensure that a wide variety of novel techniques are included.
“We expect to focus on technologies that are likely to modernise pharmaceutical manufacturing and with which both the Agency and industry have limited prior experience and knowledge,” the spokesperson says.
What this will mean for tomorrow’s manufacturing plants, time will tell.
This article appears in the April 2016 edition of Pharma Technology Focus