Drug Shortages Highlight Quality Problems

In an article written by Peter Loftus at the Wall Street Journal, a patient affected by the shortage of the cancer drug BCG was quoted as saying, “This totally took me by surprise. It was the very first time I had to think about the drug companies failing the people that they’re supposed to be there for.”  For this patient, it was the first time, but according to the article, “the number of drugs in short supply in the U.S. has risen 74% from five years ago, to about 265, according to the University of Utah’s Drug Information Service (UUDIS).”  The FDA reports the number of drug shortages as one that’s going down, from 251 in 2011 to 44 in 2014. The UUDIS and FDA may not define a shortage the same way, but they both agree the US does indeed have a problem with drug shortages.

In the WSJ article, Loftus outlined how a lack of quality oversight at the Sanofi and Merck facilities producing BCG resulted in numerous facility shutdowns (due to air quality issues and mold). And while there are a number of reasons experts could provide on why shortages still exist in 2015, this is only one of many instances where manufacturing quality issues played a role in a drug shortage. 

Dr. Janet Woodcock, director of CDER

On the same day this article was published, I watched Dr. Janet Woodcock, director of CDER, stepped up to the mic to deliver her keynote on the first day of the ISPE Quality Manufacturing Conference. The purpose of this event was to give industry professionals and regulators the opportunity to discuss how to achieve and maintain quality in pharmaceutical manufacturing. In her speech, Dr. Woodcock summarized some “major transformations on regulatory pharmaceutical quality” made by the FDA. This included overcoming challenges related to the launch of the Office of Pharmaceutical Quality (OPQ) in January of this year.

Despite understaffed offices, the OPQ was able to release an Established Conditions draft guidance last month, pilot new templates for inspectors, begin the task of tackling a GDUFA backlog in the thousands, and work toward alignment with the Office of Regulatory Affairs (ORA). The goal of these efforts is to move from a compliance-based, reactive approach to a proactive one. The risk assessment approach of Quality by Design (QbD) is one she noted as an essential concept to achieving this.

Dr. Woodcock provided a framework of current developments that are spurring change in risk assessment:

• Breakthrough therapies – If a drug is designated as a breakthrough therapy, it requires a pharmaceutical company to still deliver an adequate drug but in a shorter timeframe. “To do this, some trade-offs are required,” says Dr. Woodcock. “You have to understand what you’re trading off and what the risk of that is. It’s important to balance the risk with the needs of the patient.”
• Continuous manufacturing – Dr. Woodcock referred to this as “the future.” She added that the transition of small molecule drug development to continuous manufacturing will be quicker. This was evidenced by the focus on the innovations and progress of this sector during the event’s continuous manufacturing track.
• 21^st Century Cures Act – This Act, although still pending approval, shows the need to advance manufacturing practices is understood by Congress. Bringing innovation to the industry and retiring out-of-date manufacturing practices is imperative to bringing agility to pharma – a gap Dr. Woodcock says industry must address in order to prepare for the future.
• Lifecycle management – Dr. Woodcock explained that this concept gives a robust assurance about a company’s state of quality. “Two-to-five year inspections or waiting until something goes wrong is not enough,” she added. She urged the audience to read the WSJ article and explained that drug shortages, such as the one highlighted in the article, represent a failure of lifecycle management.

Andy Skibo, head of global biologics operations and global engineering at MedImmune/AstraZeneca, also made a push for proactive planning in his keynote the following day. Skibo challenged the audience to think about supply chain risk assessment the same way they approach quality.