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Performing a compliance gap assessment and focusing on six key factors in your facility’s process definition and controls can help your facility pass its next FDA inspection with flying colors.
FDA’s close oversight of the pharmaceutical industry through current good manufacturing practices (cGMPs), audit requirements, and rigorous approvals provides patients with a high measure of confidence that medicines and vaccines in the United States are safe and effective. But for those responsible for pharma manufacturing operations-which includes ensuring the performance and reliability of critical equipment-FDA audits can inspire worry. Often, FDA compliance requirements must be balanced against a company’s need to compete in an increasingly competitive global market full of treatment options and price sensitivities.
As in most cases, an ounce of prevention-grounded in self-knowledge and organizational awareness-is worth many pounds of cure. Any facility and company can benefit from taking a deep dive into evaluating its readiness for an FDA inspection.
When FDA finds that a pharma manufacturing facility is out of compliance with any part of the required standards for cGMPs, the agency steps in and takes action. This action may range from coaching to help the firm come into compliance to closing and condemning the facility, with many degrees of corrective measures between those two extremes.
FDA may issue a 483 or warning letter that describes any violations that inspectors found during their audit and the steps needed to address each area of concern. It then becomes the facility management’s job to determine what went wrong and how best to address each issue, and to document each remediation step in a response to the agency.
The first prerequisite for success is knowing the areas that FDA auditors will focus most closely on and how to avoid potential inspection pitfalls. Having clear, concise procedures, with practices grounded in sound engineering and rigorous reliability practices, is crucial to avoiding problems. Documenting and demonstrating adherence to these practices is equally important. Because there are so many proprietary processes specific to each individual pharma production facility, details of the processes may be entirely different from one location to another, making the importance of good documentation and adherence to methods and established procedures even more critical.
Organizational assessments, both internal and external, are the next step on this path. Knowing where a facility is in relation to the regulatory requirements and guidelines is crucial to success. A tool that is gauged to critique organizational capability, impartially, will provide a platform from which to perform a gap assessment, to examine current performance, and determine what the facility may need to work on in order to achieve compliance with cGMP regulations. This assessment must then be followed by a plan for action (and remediation, if needed), if the firm is to ensure that its next FDA audit is a success.
A number of tools are available to help measure key performance factors that affect regulatory compliance and organizational performance. They include:
Using these tools will tell show where a facility’s operations are, in terms of regulatory compliance. Whichever assessment tool a company chooses to use should not only give a clear understanding of where the facility currently is, but also form the basis for an action plan designed to improve its competitive position.
This plan should be based on the six crucial aspects of process definition and control:
Asset management is made up of the processes and disciplines that ensure that the facility’s production and other physical assets are correctly installed, supported, and documented in a correct equipment hierarchy, in a computerized maintenance management system (CMMS) and on current and correct piping and instrumentation diagrams (P&IDs). Asset management also covers the disciplines and systems that ensure that appropriate preventive and predictive maintenance and other activities are in place to preserve the lifespan and capacity of those assets.
Process control is the system of manufacturing instructions, recipes, and safeguards that any pharma production facility will use in the production of commercial products. The critical control attributes will always be consistency, accuracy, and purity for the product array.
Documentation management has everything to do with the way the organization defines itself, its processes, and the records that it must keep to demonstrate adherence to production standards and maintenance requirements. This will require strict policies for version control, a controlled data repository, and on-going employee training in how to perform standard operating procedures (SOPs) to meet regulatory requirements.
Work management is more than simply utilizing a work order system; it includes constant and deliberate examination of the sources and remedies for recurrent failures (i.e., bad actors), training on the use of non-destructive technologies, documentation and record keeping for regulatory authorities, as well as metrics that measure effectiveness, efficiency, and integration with all stakeholders in the facility.
Supply chain control is made up of those disciplines that are needed to ensure that maintenance, repair, and operations stores are kept in an appropriate environment and stocked at adequate levels to meet demand, and that appropriate security measures are in place to protect works-in-progress and finished products within the facility.
Organizational development is everything that the facility needs to ensure that the staff and management of the firm reach or remain up to date in learning, process optimization, and research and development.
In a recent project, this six-factor approach was used to analyze one pharma client’s inspection readiness. The company had received a 483 inspectional observations report from FDA, which detailed conditions and findings that put the facility at risk of receiving more severe regulatory citations in the near future. Initial assessment of the facility found a number of problems (e.g., database errors and deficiencies; work management process and PM/PdM issues).
To get a clear picture of how well the organization was managing its procedures and documentation, a five-stage response format assessment tool was used. Responses were assigned a Likert-scale value (2) and tabulated to provide a numeric score for each of the areas that were examined.
Based on the assessment and subsequent discussions with site management, the team undertook a broad-based program of process remediation. A representative response for this client is found in Figure 1.
Figure 1: An excerpt from the client’s readiness assessment survey.
Planners are prepared to do field investigations and prepare appropriately detailed plans for the execution of maintenance work.
The primary components of our program for this client included:
After the above assessments were completed, a data-collection tool specific for the facility was designed, then staff was trained to use the tool. Staff members were assigned to physically inspect and collect data in different areas of the facility based on each area’s accessibility and order of importance. Some areas were only accessible during shutdown and had to be scheduled around cleaning schedules.
As audits of each area within the facility were completed, the plant’s assets were ranked based on associated equipment and the importance of their placement in the sequence of production operations. Each significant asset (including all instrumentation and control devices) was examined for impact on the process and products.
Based on pre-determined criteria, each asset was assigned a risk value. This value was later used to identify the level of preventive and predictive maintenance support that wold be most appropriate for that asset.One of the primary concerns in performing the walk-down effort was to standardize the level of detail being gathered in the data-collection tool, and to ensure that all of the CMMS data entry was kept current with the field efforts. Omissions and errors in the P&IDs were noted and referred to site engineering for correction on a system-by-system basis.
The work management process was examined and, in cooperation with site engineering, was revised to ensure that all portions of the process were addressed. Specific responsibility, accountability, consulted, and informed (RACI) matrices (3) and processes were designed and documented for:
All of the activities were controlled from within the resident CMMS system.
Since these efforts, the facility’s production has stabilized. Fewer batches are being held for inquiries, and there has been a marked reduction in downtime associated with equipment failure. As a result, the FDA 483 has been lifted, and the facility is in a better position to avoid regulatory noncompliance issues in the future.
Management and employees now embrace a rigorous process for introducing and documenting new assets into the facility’s process hierarchy. In addition, since the project was completed, workers have a much better understanding of the roles that they and their colleagues play within the facility, resulting in better communication and cooperation between departments. Documentation of predictive and preventive processes has improved, and standard work plans are being used where needed. The facility is now positioned to adapt for the future, provide safe and reliable products to market, and improve training programs for employees on the SOPs that are required to run the plant in a compliant manner.
1. C. Vinney, “Likert Scale: What is It and How to Use It,” thoughtco.com, June 3, 2019.
2. J. Campbell and A. Jardine (Eds), Maintenance Excellence: Optimizing Equipment Lifecycle Decisions (Marcel Dekker, Inc., New York City, NY, 2001).
3. S. Haworth, “Create a Reponsibility Assignment Matrix Chart (RACI Chart) that Works,” thedigitalprojectmanager.com, January 2018.
Supplement: Outsourcing Resources
When referring to this article, please cite it as C. Spillman, “Why Dread Your Next FDA Inspection?" Pharmaceutical Technology Outsourcing Resources Supplement (August 2019).