OR WAIT null SECS
This year promises to bring more focus on risk management and building a quality culture, says consultant Susan Schniepp.
Although the impact of the US federal government shutdown remains unclear (1), leaders within FDA say they are encouraged by the progress made within the agency and industry during 2018.
According to reports published by the Regulatory Affairs Professionals Society (RAPS) (2), Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research (CDER), singled out generic drugs as a key area where improvement was seen in 2018. She noted an increase in productivity in new molecular entity (NME) development and review at the FDA/Centers for Medicare and Medicaid Services Summit in Washington, D.C. on December 11, according to RAPS.
For 2019, the report said, Woodcock’s top manufacturing and quality-related priorities for CDER include:
FDA Commissioner Scott Gottlieb, speaking at the FDLI Enforcement Litigation and Compliance Conference on Dec. 12, 2018, emphasized the importance of risk-based inspection and efforts to ensure that the regulatory burden placed on drug manufacturers is aligned with public health priorities (3). Gottlieb also noted efforts to strengthen FDA’s Office of Regulatory Affairs (ORA) mentioning a program designed to integrate ORA and CDER more closely. He also spoke of global inspection harmonization, singling out the Mutual Reliance Agreement (MRA) with the European Union. An example of MRA in action that he pointed to is the International Active Pharmaceutical Ingredient Inspection Program, which was recently used to share information on valsartan API facility inspections.
For manufacturers and quality specialists, what were the key regulatory achievements in 2018, and what issues promise to dominate this year? Susan Schniepp, executive vice-president of post-approval pharma and distinguished fellow at Regulatory Compliance Associates, shared some insights with Pharmaceutical Technology.
PharmTech: What key regulatory trends do you expect to take shape for 2019?
Schniepp: Many of them will focus on quality. The fact that FDA is rethinking its quality metrics program, and that the agency asked for sites to volunteer to be inspected in 2018, was pretty significant. We don’t know what FDA’s final program is going to look like, but we did see signs in its data integrity guidances that FDA would be increasing its attention on how manufacturers approach the task of building a quality culture.
This emphasis will bring FDA more in line with other global agencies, which did not jump on the quality metrics bandwagon but have been more interested in quality culture issues.
PharmTech: Were there weaknesses in FDA’s original quality metrics plans?
Schniepp: The agency will continue to tie quality metrics to drug shortages, which will still be an issue in 2019. This approach makes sense, since, once we see metrics, we can do surveillance to identify where problems are developing and how these problems can be deflected, diverted, and remediated before they develop into drug shortages.
However, the metrics that FDA originally selected (e.g., corrective and preventive action [CAPA] turnaround time) were lagging rather than leading ones. The industry would benefit more from metrics that indicate when facilities are heading into a problem (e.g., scrap rates, which signal manufacturing problems and tie in closely to the issue of aging facilities).
PharmTech: Will aging facilities receive more attention from the industry and regulators in 2019?
Schniepp: This issue will continue to play out in 2019. At the Parenteral Drug Association (PDA), we’ve spent a lot of time working on post-approval changes, to allow manufacturers to get regulatory relief so that they can modernize facilities more easily. Until this process becomes easier, we will continue to see problems with aging facilities and a rise in scrap rates, reject rates, and aborted lots. These are the metrics that should be tracked.
There are also cost-vs-benefit questions [that tie into drug recalls and commodity drug shortages] and fit right into the aging facilities problem. For example, manufacturers may ask, 'Why modernize a sodium chloride line when it will not bring any profit?'
PharmTech: PDA has been actively involved in a number of regulatory issues and in communicating with FDA. Where has PDA made the greatest progress in this regard in 2018?
Schniepp: One important achievement was the development of best practices for laboratory data integrity, and PDA is now working on best practices for manufacturing data integrity, encompassing not only computerized and hybrid, but paper-based systems. It’s so interesting that data integrity keeps coming up as an issue for pharmaceutical manufacturers. Even though the industry went through this in the 1980s with the Barr decision, data integrity continues to rear its head.
PharmTech: What are the greatest challenges ahead and building a quality culture within the industry?
Schniepp: Investigations into CAPA, things that have gone wrong, and deviations, will continue to be significant problems. Another looming challenge is the fact that, as we move forward with individualized stem and gene therapies, quality risk-based decision making will also have to advance.
These issues will challenge the traditional quality professional. How will one release a lot, for example? And how will investigations into manufacturing problems proceed on site? How is quality going to integrate with manufacturing, so that we get out of our desk chairs and perform lab and site investigations in real time as problems happen, and ensure that the results are meaningful?
PharmTech: Do you expect a framework analogous to current good manufacturing practices (CGMP) to be brought to bear on compounders?
Schniepp: It will be interesting to see how FDA manages compounding pharmacies in 2019. Remember, these facilities are essentially making uncontrolled drugs. They don’t have a new drug application (NDA) or filing associated with them, yet a number of large compounding companies are making large lots of product and sending it to hospitals, as permitted by 503b of the Drug Quality and Security Act.
Some of the guidelines that surround traditional aseptic processing are new to them (e.g., they are performing manual manipulations of product under a hood), yet they may not understand why they need to do a media fill or why a particle count is important.
They may also fail to understand how final product testing relates to production and what a certificate of analysis really means. Another question is how should they approach stability? Traditional manufacturers work on container closure issues, but compounders are manipulating closures, and often their product expires within 90 days.
1. Pharmaceutical Technology editors, “Critical FDA Functions Continue as US Government Shutdown Hits the One-Week Mark,” pharmtech.com, Dec. 29, 2018.
2. Z. Brennan, “Woodcock Lays Out Top CDER Priorities for 2019,” raps.org, Dec. 12, 2018.
3. S. Gottlieb, “Remarks By Scott Gottlieb at the FDLI Enforcement Litigation and Compliance Conference,” fda.gov, Dec. 12, 2018.
Vol. 43, No. 1
When referring to this article, please cite it as A. Shanley, "Data Integrity Topped 2018 Priorities," Pharmaceutical Technology 43 (1) 2019.