Managing Regulatory Inspections: A CDMO Perspective

May 6, 2016
Inspection success begins with awareness of the challenges and obstacles, and continues with ongoing preparation and frequent inspection readiness

When it comes to being prepared for an inspection from a regulatory authority, the combination of practice and preparation will often make the difference between success and failure. Contract Development Manufacturing Organizations (CDMO) that are routinely successful in these inspections are aware of the pitfalls and obstacles and incorporate a plan for compliance into their company culture. The chances for success increase greatly in those companies where awareness of how to achieve a successful inspection is a priority. And while it is possible that a CDMO could get through one or two inspections, it is unlikely their success will continue if they do not stay abreast of what regulatory authorities are demanding to achieve compliance. Having a regulatory inspection that is a positive experience begins with awareness of the challenges and obstacles, and continues with on-going preparation and frequent inspection readiness practice. Following are some key considerations from a CDMO perspective on how to successfully manage a regulatory inspection.

The rapid increase in the complexity of drug compounds and, in particular, biotechnology drugs, has led to a significant change in the way the international drug industry is regulated. Implemented policy changes by the FDA and other worldwide regulatory authorities have led to an increase in the number of inspections of sterile contract manufacturers. These inspections have not only changed in their frequency. The actual degree of vigilance by inspectors in certifying that all processes and procedures meet stringent quality control will further increase. This regulation should not be viewed as a negative. After all, increased regulation of the industry has led to even stronger quality control systems, safer medications for the patients who rely on them, and a more positive view of the industry as a whole. Successful companies are those that are aware of, and prepared for, the changes in the regulatory climate and the challenges that must be overcome in achieving a successful inspection.

Regulatory agencies are increasing their vigilance on the (bio-)pharmaceutical industry with greater scrutiny placed upon aseptic manufacturing facilities. Perhaps one of the most significant changes in this attentiveness has been in the area of data integrity. A recent increase in the number of incidents where a company’s data was falsified or poorly documented has led to new regulations from the British authority MHRA (Medicines and Healthcare products Regulatory Agency) and the WHO (World Health Organization). In the near future, there will also be a revised Annex 1 to the EU GMPs Guideline. If regulatory authorities are going to be more observant and stringent in their review processes, contract manufacturers must, in turn, be even more vigilant and stringent in their data documentation. Any existing or potential minor issue must have an immediate corrective action with a demonstrated, short-term positive outcome.

Inspections by regulatory authorities, particularly the FDA, can be a challenging experience, especially when the number of inspectional observations and increased enforcement actions resulting from these inspections grow. To help reduce the challenges inherent in an inspection, it is essential to continuously remain in contact with regulatory authorities. Cooperation with local authorities, as well as participating in meetings with the FDA concerning quality metrics is critical. Every effort should be made to remain current with any new thoughts or actions about regulation that the authorities may be considering. In some cases, CDMOs may also have to make additional investments in equipment, personnel and process optimizations.

The pharmaceutical industry is one of the most highly regulated branches. This is normal given the nature of the work that the industry is involved in. Thus, it stands to reason that one should not expect that the level of regulation will change at any time in the near future. Working hard to stay abreast of what regulatory authorities expect and trying to anticipate what they are considering for the future is the key to managing the increase in regulation.

Therefore, actions must be taken that help manufacturers anticipate and meet the future demands of international regulatory authorities. The continual improvement of systems to achieve the high level of quality that meets international regulatory standards is the goal. Looking for the root causes of issues and taking corrective actions that are appropriate, while demanding tight quality control by suppliers, will support enabling that any product used in manufacturing meets exacting standards. In relationships with suppliers it means that the production processes they employ are carefully reviewed, risk assessment is quantified and controls are put in place. Continuous development of manufacturing sites and techniques to prepare them for future needs and requirements is necessary for manufacturers to deal with increasing regulatory requirements. If systems are not according to regulations, (bio-)pharmaceutical companies may have difficulty entering markets that are regulated by these authorities.

Contract manufacturers that are confident in what they do react calmly and with confidence to an inspection. Those that follow proper procedures will be in a promising position to manage the inspection process and handle the increase in regulatory oversight.

Joachim del Boca earned his degree as a certified engineer in 1975 from technical college, and graduated from the University of Munich/Pharmacy in 1981 as a licensed pharmacist. He began his career as a pharmacist in a public pharmacy in 1981 and joined Vetter in 1983 as Assistant to the Director of Production. He has held positions including Director of Production, and VP of Quality Assurance before being appointed to his current position in 2012.

About the Author

Joachim del Boca | VP of Regulatory Affairs/Quality Compliance