While other industries have completely modernized the way they manufacture their products, the biopharma industry, in large part, is stuck in the "this is how we've always done it" mode.

To help change that, regulators across the world are going to have to streamline their current Rube Goldberg approach to regulating quality throughout a drug's lifecycle. As a result of the variety of regulatory schemes, it can take a drug company three to five years to globally implement a routine chemistry, manufacturing and control (CMC) improvement, Ashley Boam, director of the FDA's Office of Policy for Pharmaceutical Quality, said at the agency's Pharmaceutical Quality Symposium Wednesday.

The disharmony in regulatory standards results in manufacturers needing to maintain multiple inventories, which adds to costs and may cause supply disruptions, Boam said. Such time-consuming, costly obstacles can dissuade manufacturers from making improvements that would ensure consistency in pharmaceutical quality.

To bring drug manufacturing into the 21st century and support industry in developing and implementing innovative approaches to ensure quality in drug production, the FDA is identifying and resolving potential scientific and regulatory barriers, said Patricia Cavazzoni, deputy center director for operations at the FDA's Center for Drug Evaluation and Research (CDER).

One big step will be the implementation of the International Council for Harmonisation's (ICH) Q12 guidance on technical and regulatory considerations for pharmaceutical lifecycle management. The guidance is intended to dismantle some of the harmonization hurdles that are obstructing the modernization of drug manufacturing.

Recognizing that the discord among regulatory practices is an obstacle, ICH proposed Q12 to encourage innovation and continual improvement in manufacturing processes by providing a framework to streamline the management of post-approval CMC changes in a more predictable and efficient manner.

Boam said the guidance is expected to provide manufacturers with greater clarity regarding which elements of the control strategy must be reported if changed, how much flexibility exists within an identified established condition and how to report changes to those conditions.

The guidance also would allow for greater regulatory flexibility in managing post-approval manufacturing changes by using the knowledge about the product and manufacturing process gained through the development and commercial manufacturing experience. That knowledge is expected to reduce the number of change submissions.

Making the move to Q12 won't be easy. "It will almost be like turning a cruise liner around," CDER's Mahesh Ramanadham said. To prepare for that undertaking, CDER's Office of Pharmaceutical Quality (OPQ) has been training its staff on Q12 for the past year and a half, Ramanadham added.

Regulators will begin implementing Q12 after the various experts sign off on it. That sign-off is expected next month. In the U.S., implementation will require the FDA to publish Q12 as a final guidance.

Meanwhile, the agency is taking several other steps to bake pharmaceutical quality into the drug manufacturing process. Last year, CDER published a dozen guidances on drug quality, which OPQ Director Michael Kopcha defined as ensuring every dose of a drug is safe, effective and free of contamination.

CDER also published seven drug quality documents for its Manual of Policies & Procedures in 2018 and responded to 554 controlled correspondence and 230 external inquiries on drug quality issues, Boam said. So far this year, CDER has released one final and four draft guidances dealing with quality control. In addition, a revised draft guidance is expected this week on drug master files, and several others are due out within the next few months.

Besides the new guidances, Boam said CDER is reviewing more than 150 existing quality-related guidances for relevance, effectiveness and needed improvements.

But quality isn't just up to CDER; industry has to play its part, as well. "Pharmaceutical quality is a shared responsibility" that requires collaboration, innovation, communication and engagement, Kopcha said.

Despite CDER's ongoing focus on quality, inadequate quality unit oversight continues to be one of the top three problems found in FDA inspections of manufacturing facilities, OPQ's Rakhi Shah said. The other two are equipment problems and production and process controls.

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