FDA has been implementing the Safety and Innovation Act since it was passed by Congress in 2012. The Act requires FDA to establish Mutual Recognition Agreements (MRAs) which are agreements between two or more countries to recognize a specific process or procedure of the other country. The FDA’s MRA was preceded by the 1998 signing of the U.S. and the EU Agreement on Mutual Recognition which included a Pharmaceutical Annex providing for recognition of each other’s GMP inspections. Unfortunately, this Annex was never fully implemented.
Effective in 2017, the amended Sectoral Annex to the 1998 U.S.-EU MRA allowed for inspection reports and other related information obtained during drug manufacturing facility inspections, conducted by either an EU inspectorate or by FDA, to help determine whether a facility is manufacturing high-quality drugs. If more information is necessary beyond this assessment, FDA or the EU can then require additional inspections or take other action in the interest of protecting the public.
The 2017 Annex provides for greater efficiency in the drug inspection process, eliminating the redundancies of duplicate facility inspections, particularly those with a strong record of compliance. By utilizing each other’s inspection reports and related information, the FDA and EU are able to reallocate resources towards inspection of drug manufacturing facilities with potentially higher public health risks across the globe, benefiting patients and reducing adverse public health outcomes.
FDA’s determination as to whether an MRA is appropriate is made first via an assessment of internal audits in a particular EU country to ensure that their inspectorate is functioning properly and not deviating in any significant way from EU law and guidance.
These audits include observations of drug manufacturing facility inspections conducted by the audited inspectorates and utilize the 78 indicators based on the Pharmaceutical Inspection Co-operation Scheme (PIC/S) compliance assessment program with an EU addendum. PIC/S is an internationally recognized cooperative arrangement between 49 regulatory authorities, including the FDA. The goal of PIC/S is to harmonize inspection procedures worldwide and develop common standards in the field of good manufacturing practices.
In addition, FDA considers any conflict-of-interest policies, specific legislation related to good manufacturing practices, samples of inspection reports, inspector training records, inventory of drug manufacturing facilities, surveillance program, and numerous standard operating procedures to evaluate a pharmaceutical inspectors’ credentials as part of the capability assessment of each EU country. In this way, FDA can ascertain whether the inspection authorities are trained and qualified and have the skills and knowledge to identify manufacturing practices that may lead to patient harm. Maintenance provisions are also included in the Annex to ensure that each capable country continues to meet FDA requirements.
Thanks to this MRA, there is a greater ability of the Agency to appropriately allocate its resources to focus on those facilities where initial audits raise red flags that warrant further inspection, either by continual deficiencies in inspection findings by a country’s own internal audit system or by adverse events reports or other means. One of those means is the “Drug Quality Sampling and Testing (DQST)- Human Drugs Compliance Program 7356.008”, which is a surveillance program that samples and tests pharmaceutical products manufactured both in the U.S. and foreign countries. Surveillance under the DQST is prompted in part by recommendations from CDER and ORA headquarters and FDA district offices based on their intelligence and reported consumer complaints.
The goal of the DQST compliance program is to protect the public health by minimizing exposure to non-compliant and/or poor-quality drugs. Testing is undertaken on finished dosage forms, APIs, and excipients and the samples chosen are based on risk-based selection criteria and a risk-based model. Due to the globalization of pharmaceutical products increasing consumer risk, the surveilled domestic and international products have expanded under this program to include prescription and OTCs, compounded drugs, drug products with approved an NDA or ANDA as well as unapproved drug products and others. This program, in combination with other quality assurance compliance programs, is an integral part of the Agency’s overall post-marketing surveillance strategy. Fortunately, the majority of drugs FDA independently tests meet their specifications. From 2003 to 2013, FDA tested nearly 4,000 of drug samples. During that decade, FDA laboratories found that 1.1% of the drug products analyzed deviated from acceptable standards.
FDA takes its oversight of the domestic and foreign pharmaceutical program very seriously as any safety deviations in these products could have a significant impact on public health. Companies may wish to proactively perform quality assessments and gain an understanding of their current compliance status through independent third-parties such as qualified consulting firms who offer expertise in pharmaceuticals conducted by persons with a strong background in Agency regulations and safety standards. Once a needs assessment has been conducted, a proactive remediation plan of deficiencies can begin.
More information on FDA’s pharmaceutical surveillance programs can be found on the Agency’s website and we invite you to view EAS-produced on-demand webinars focusing on a variety of GMP tools on the EAS website. Should EAS be of service to your firm either in an assessment of compliance status or to assist with an FDA announced facility inspection, please contact Bryan J. Coleman, Senior Director of Pharmaceuticals and Medical Devices.