The Parenteral Drug Association (PDA) and the U.S. Food and Drug Administration (FDA) once again cosponsored the 2022 PDA/FDA Joint Regulatory Conference with the theme, “Quality Evolution/Technology Revolution: Modern Quality Management Solutions.”
Due to the COVID-19 pandemic, there became a pressing need to address the public health crisis, which led to some introspective thinking among industry and regulators about improving communication and embracing innovation and technology. This emphasis on improvement was the overarching message from the PDA/FDA conference.
During the session, speakers from the pharmaceutical industry addressed the need for early and frequent communication with regulators. Moderna’s Chief Technical Operations and Quality Officer Juan Andres shared that the company chose to proactively present its quality risk management approach to the agency when developing its COVID-19 vaccine rather than waiting for the agency to demand it from them. As a result, the FDA allowed a stepwise approach based on risk.
Other industry representatives shared how communication and collaboration with regulators helped to minimize supply disruption during the pandemic.
Better communication is equally important as the FDA seeks to deepen its understanding of new technologies and the science behind them.
Learning from the Pandemic
Presenters revealed the challenges they faced during the pandemic and how their overall learning from it may facilitate significant advances in the product development space. For instance, in the race to develop a vaccine for COVID-19 before it mutated, innovative companies had to think beyond what was possible and not accept the impossible.
As Andres noted in his presentation, Moderna encouraged its teams to “act with urgency, obsess over learning, question convention, accept risk and digitalize wherever possible.” Many companies have found that digitalizing and modernizing is key to giving innovator companies rapid access to data so they can adjust quickly.
Modernizing and collaboration are equally important to regulators, especially when working with new technologies. While regulators have always been open to knowledge-sharing from the industry, they have stepped up efforts to encourage more collaboration as they seek to better understand the science behind such new innovations as cell and gene therapies and harmonize regulations and risk-based approaches to regulating new products.
Driving Business Continuity
Another theme that emerged from the conference was the importance of having a quality management maturity model. This is about having a quality culture that goes beyond simply measuring metrics but emphasizes keeping facilities updated, ensuring business continuity and moving beyond regulations.
The quality management maturity (QMM) program that FDA’s Center for Drug Evaluation and Research (CDER) is described as “the state attained when drug manufacturers have consistent, reliable, and robust business processes to achieve quality objectives and promote continual improvement” (1).
Integral to this approach is what one FDA speaker referred to as “sustainable compliance,” meaning to aim higher with compliance and not “target the minimum.” As they explained, when targeting at the minimum or the average means, sometimes processes will fall below the minimum, leading to compliance failures. To avoid or limit these failures, leadership must establish a quality culture in daily decision-making.
Improving Partner Oversight
Speakers also addressed the importance of proper collaboration with and oversight of key partners, particularly contract manufacturing organizations (CMO), to assure project success. Proper oversight begins with selecting the right CMO for the company’s products and needs and formalizing expectations upfront. It requires compatible quality systems to ensure continuous and seamless communication between the CMO and the vendor. Data should be constantly monitored to ensure objectives are met, and a risk-based approach should be adopted to oversee outcomes.
Integral to that constant communication and monitoring is having technology solutions that enable data to be shared in real time and ensuring your CMO is willing to use those solutions.
Having good processes in place with your CMO will also be key to supporting hybrid regulatory assessments. During the pandemic, FDA adopted the use of remote assessments and increasingly has been open to hybrid assessments where documentation is reviewed remotely, allowing less time to be spent on site to inspect the facility design, flow and personnel activities. This is a change from prepandemic practices when FDA would typically spend one or two weeks on site. This hybrid approach feeds into the QMM approach, whereby if the CMO has a good quality management rating, off-site or virtual inspections may continue.
However, the agency has advised that, as the pandemic winds down, they intend to do more on-site inspections while remaining open to the off-site review of documents.
During the conference, the Center for Biologics Evaluation and Research (CBER) noted that some quality issues continue to be raised year after year, including the failure of the Quality Control Unit to perform its duties, computer systems violations and investigation deficiencies.
Contamination Control Strategy Reviewed
For its part, PDA provided speakers who reviewed their interpretation of the PDA approach to contamination control strategy (CCS) and indicated that PDA’s Technical Report No. 90: Contamination Control Strategy Development in Pharmaceutical Manufacturing. should be available before the end of year. The presentation emphasized a systems approach to CCS with clear documentation on prevention, remediation and monitoring to ensure patient safety.
TR-90 comes in the wake of the European Union’s revision of Annex 1, which was published in August 2022 and requires the use of the CCS. Earlier last year in 2022, PDA addressed the benefits of following the more holistic approach proposed by the Annex 1 revision, which states “Processes, equipment, facilities and manufacturing activities should be managed in accordance with QRM principles to provide a proactive means of identifying, scientifically evaluating and controlling potential risks to quality” (2).
The FDA’s Draft Guidance for Industry: Inspection of Injectable Products for Visible Particulates (Dec. 2021) was also reviewed during the conference. A discussion revolved around how CCS should address particulate contamination and how the visual inspection process adds to the control or detection needed to prevent this type of contamination from reaching the patient. As with Annex 1, the emphasis on a holistic, proactive approach–the objective behind the visual inspection guideline–is to have the oversight needed to know what is normal for your process and react if limits are exceeded.
Connecting Industry and Regulators
Joint conferences such as those held by PDA and FDA provide learning opportunities for industry and regulators alike. Innovation and technology, together with better communication, can advance the goal of quality assurance to the benefit of all stakeholders.
- CDER Quality Management Maturity, https://www.fda.gov/drugs/pharmaceutical-quality-resources/cder-quality-management-maturity
- Annex 1: Manufacturing of Sterile Products, https://health.ec.europa.eu/system/files/2020-02/2020_annex1ps_sterile_medicinal_products_en_0.pdf
About the Author
Londa Ritchey is the Quality Director at PharmaLex with the Quality Management and Compliance group. Londa has 30 years of experience in pharmaceutical/bio pharmaceutical quality assurance, including supplier quality management, quality risk management, aseptic quality operations, quality systems implementation and contamination risk management. She has been engaged with large and small firms through all phases of drug and biologics lifecycles.