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What are Quality Metrics (QM)?
QMs are an objective way to measure, evaluate, and monitor the product and process lifecycle. Quality metrics data may lead to higher levels of safety, efficacy, delivery, and performance.
Quality metrics are used throughout the drug and biological product industry to monitor processes and drive continuous improvement efforts in manufacturing. Effective use of quality metrics is one characteristic of robust site Quality Management Maturity (QMM).
Why are Quality Metrics Important?
The minimum standard for ensuring that a manufacturer’s products are safe, effective and of sufficient quality is compliance with current good manufacturing practice (CGMP) requirements. CGMP compliance alone, however, does not indicate whether a manufacturer is investing in improvements and striving for sustainable compliance, which is the state of having consistent control over manufacturing performance and quality. Sustainable compliance is difficult to achieve without a focus on continual improvement.
An effective Pharmaceutical Quality System (PQS) ensures both sustainable compliance and supply chain robustness. Quality metrics can contribute to a manufacturer’s ability to develop an effective PQS because these data provide insight into manufacturing performance and enable the identification of opportunities for updates and innovation to manufacturing practices. Quality metrics also play an important role in supplier selection and can inform the oversight of contract activities and material suppliers, as well as help determine appropriate monitoring activities to minimize supply chain disruptions. Quality metrics data from establishments can also have utility to the FDA:
Assist in developing compliance and inspection policies and practices.
Improve prediction and possibly mitigation of future drug shortages, while encouraging the pharmaceutical industry to implement innovative quality management systems for manufacturing.
Enhance FDA’s risk-based inspection scheduling, reducing the frequency and/or length of routine surveillance inspections for establishments with quality metrics that suggest sustainable compliance. Provide ongoing insight into an establishment’s operations between inspections.

How Can Quality Metrics be used at FDA?
As part of FDA’s ongoing adoption of risk-based regulatory approaches, the agency is proposing to develop and implement a Quality Metrics Reporting Program to support its quality surveillance activities. Under this program, the FDA intends to analyze the quality metrics data submitted by establishments to:
obtain a more quantitative and objective measure of manufacturing quality and reliability at an establishment; integrate the metrics and resulting analysis into FDA’s comprehensive quality surveillance program; and
apply the results of the analysis to assist in identifying products at risk for quality problems (e.g., quality-related shortages and recalls).
Background on FDA’s QM Program
In 2004, FDA issued the report “Pharmaceutical CGMPs for the 21st Century – a Risk-Based Approach”. In 2014, FDA gained additional insight when the Brookings Institute collaborated with FDA to convene an expert workshop, “Measuring Pharmaceutical Quality through Manufacturing Metrics and Risked-Based Assessment”, which provided an opportunity for pharmaceutical manufacturers, purchasers, regulators, and other stakeholders to discuss the goals, objectives, and challenges for a pharmaceutical QM program.
In July 2015, FDA issued the draft guidance Request for Quality Metrics (80 FR 44973), which described a proposed mandatory program for product-based reporting of quality metrics. Under this program, manufacturers would have submitted four primary metrics. Stakeholder comments on the guidance included concerns regarding the burden associated with collecting, formatting, and submitting data at a product level across multiple establishments; technical comments on the proposed metrics and definitions; and legal concerns regarding the proposed mandatory program. Stakeholder commenters also suggested a phased-in approach to allow learning by both industry and FDA.
In response to this feedback, FDA published a revised draft guidance in November 2016 entitled Submission of Quality Metrics Data (81 FR 85226). The 2016 guidance described an initial voluntary phase of the QM Reporting Program, with participants reporting data either by product or establishment, through an FDA submission portal. FDA removed one of the four metrics from the 2015 draft guidance and requested submission of the remaining three key metrics. This 2016 guidance also described how FDA intended to utilize the submitted data. Commenters requested a better understanding of the value and utility of the data to be submitted to FDA and how FDA would measure success of the program. Commenters also expressed a preference for a pilot program to gather industry input before implementing a widespread Quality Metrics Reporting Program.
In Federal Register notices issued in 2018, FDA announced the availability of two pilot programs, a Quality Metrics Site Visit Program (83 FR 30751) and a Quality Metrics Feedback Program (83 FR 30748) for any establishment that had a quality metrics program developed and implemented by the quality unit and used to support product and process quality improvement. Additional information and lessons learned by FDA can be found on the FDA Quality Metrics Reporting Program; Establishment of a Public Docket; Request for Comments.
In March 2022, FDA established a docket to solicit comments on changes to FDA’s previously proposed Quality Metrics Reporting Program. This notice describes considerations for refining the Quality Metrics Reporting Program based on lessons learned from two pilot programs with industry that were announced in the Federal Register in June 2018, a Site Visit Program and a Quality Metrics Feedback Program, as well as stakeholder feedback on FDA’s 2016 revised draft guidance for industry Submission of Quality Metrics Data.
Common Compliance Issues in the Pharmaceutical Industry (and How to Avoid Them)
The US FDA releases an annual report summarizing observations from inspections by industry. The pharma industry in 2018 received 3,344 observations for 390 categories of noncompliance. Almost a third of these observations (39% of them) can be divided into just ten categories, thus illustrating the common challenges of pharmaceutical compliance.
However, the results become even more apparent when you group the data into categories based on the top ten reasons.
The four-and-a-half-dozen organizations received a 483-letter relating to noncompliance for creating or following procedures or problems with record-keeping. Additionally, 322 of the pharmaceutical industries had difficulty designing and implementing adequate controls, and 137 had trouble maintaining their products.
Whenever a pharmaceutical startup or scale-up approaches market approval, it is customary to go through growing pains. A laboratory manager may discover that a batch of maintenance records was not reviewed the week before he went on vacation, for example, even though your means of doing things seem to be working. Fortunately, there is an easier way to handle an FDA inspection than simply hoping for the best.
1. Lack of Clearly Defined Procedures and SOPs
In a Standard Operating Procedure (SOP), clear steps are outlined for carrying out specific tasks in the workplace. Using an SOP simplifies communication and makes it easier to perform the necessary functions for the work to move forward. However, compliance issues tend to arise due to a lack of effective SOPs/Written Procedures.
Various issues prevent creating and using SOPs, including complicated language, lack of standardization, and inadequate training.
Related Articles: Workplace Productivity Depends on Employee’s Training and Development
2. Inadequate Maintenance Facilities
During 2018, more than 2% of the FDA observations were for inadequate cleaning, sanitizing, and maintenance. Sanitizing, maintaining, and cleaning equipment and utensils appropriately must comply with the FDA Code of Federal Regulations.
The company should clearly outline the methods for cleaning and maintaining hygienic conditions. For example:
Providing clear instructions for cleaning.
Indicating who is responsible.
Planning your cleaning schedule.
Providing the guidelines for maintaining the equipment properly.
Ensuring regular inspections and protective measures for equipment.
Additionally, it is essential to maintain cleaning activities logs and update them as often as other operational logs.
3. Not properly utilizing data
Real-time access to data allows companies to stay abreast of changes in compliance and improve performance. By doing this, an organization can minimize the effects of non-compliance effectively. Unfortunately, one of the key reasons that organizations cannot utilize the available data is outdated technology.
Compiling data from legacy systems is challenging. Most legacy systems provide incorrect data, and integrating new data is a complex process. It further keeps pharma companies from compliance reporting. Organizations often lack adequate reporting systems. To solve this problem, they use manual reporting systems, but they are susceptible to error. Additionally, the long-term costs are high. Companies should prioritize compliance needs and failing to do so could have dire consequences.
4. Inadequate laboratory control
About 4% of all FDA observations in 2018 concerned failed laboratory controls. To maintain the laboratory data, it is necessary to monitor and maintain the laboratory controls. In addition, raw data can help determine many items, from instrument calibration to employee compliance to SOP adherence- which can prevent problems from arising.
5. A lack of communication and collaboration
A SOP without clarified roles and responsibilities creates ambiguity. The employee is better able to perform their duties and remain compliant with standards if they correctly understand what is expected of them. Moreover, providing compliance training at regular intervals keeps them prepared for the unforeseen challenges they may face in their tasks. It would be best if you equip them with tools so they can communicate, collaborate, and learn new skills. For example, you can utilize a next-generation training management software to manage employee training while giving them a centralized platform to communicate and collaborate.
6. Participation among departments is low.
Developing an SOP isn’t a linear process. You must update it to keep it current. It shouldn’t be the responsibility of one department to create and maintain these documents. To ensure that the SOPs remain relevant, departments that use them need to collaborate and update them as required. In addition to encouraging feedback, employees will offer suggestions for improvements. It will help maintain a culture of quality and continuous improvement. You may need a good Change Control Software to manage changes in processes, documents, facilities, and more.
7. Faulty Product Review Records
To avoid omissions, the review and investigation processes must be clearly defined. Several ways are available for organizations to become out of compliance with CFR 211.192, which include:
Failure to perform a thorough log review
Reviewing downtime, cleaning, and clearance logs is a must
Process failures
Lab workers can’t examine their records
Lack of standardization
An operational team and the quality control unit should use a single set of standards and standard operating procedures for batch record review to prevent any misunderstandings.
It is unacceptable for a pharmaceutical company to receive a 483-letter due to its first FDA inspection. The 483 letter signifies that your organization is out of compliance, even if you have corrected the problem. The long-term costs of uncorrected quality and operational issues outweigh the cost of continuously following FDA best practices.
The causes of noncompliance with cGMP are rarely willful. Typically, 483 observations are the result of oversights. This may be the case as the laboratory manager forgot to review maintenance records after a week on vacation. An older copy of the SOP may be used by lab employees who lost the updated document. A broken workflow or collaboration may result in noncompliance issues or simply human error. Fortunately, your quality management system can help you avoid many of these issues.

Do you worry about getting an FDA 483 Form letter or a warning letter?
A Form 483 observation and a Warning Letter are not the same.
A Form 483 is a preliminary notice of potential violations observed during an FDA inspection, while a Warning Letter is a more serious, formal enforcement action taken when observations from a 483 are not adequately addressed, and it signals the potential for greater consequences. The 483 is an informal discussion tool between the FDA investigator and the company, whereas the Warning Letter is a formal, public document that requires a prompt and adequate corrective action plan.
FDA Form 483 (Notice of Inspectional Observations): A document provided by an FDA investigator at the end of an inspection, listing conditions that appear to violate the Food, Drug, and Cosmetic Act or other regulations.
• Purpose: To discuss the findings with the company and provide an opportunity for them to provide information or take corrective actions.
• Seriousness: Less severe than a Warning Letter; it is not a final determination of a violation.
• Publicity: Generally not made public, although they can be purchased.
• Requirement to Act: A company is encouraged to respond with corrective actions but is not legally obligated to act on the observations.
FDA Warning Letter: A formal, written notification from the FDA to a regulated company detailing significant violations of FDA regulations.
• Purpose: To formally state the severity of the violations and indicate the FDA’s intent to take further enforcement action if the company fails to promptly and adequately resolve the issues.
• Seriousness: A significant escalation from a 483, indicating serious compliance failures that may impact public health.
• Publicity: A public document that is posted on the FDA website.
• Requirement to Act: A company is legally required to address the concerns and make necessary changes
A warning letter is a formal, written communication from an employer to an employee/ a regulatory agency to a company, detailing a specific violation of policies, rules, or laws. Its purpose is to formally document misconduct or performance issues, clearly state expectations for improvement, and outline the consequences of not taking corrective action, such as further disciplinary measures or legal action. Warning letters serve as a record of the issue and provide a formal opportunity for the recipient to address and resolve the problem.
• Purpose: To formally address performance problems or violations of company policy that an employee needs to improve.
• Contents: Should include the specific issue, factual examples, dates, the impact of the behavior, clear steps for improvement, and potential consequences like termination.
• Goal: To give the employee a documented opportunity to correct their behavior and prevent future issues.
Key characteristics of a warning letter:
• Formality: Uses a formal tone and often requires a signature to acknowledge receipt.
• Specificity: Clearly outlines the exact issue and provides concrete examples, dates, and relevant details.
• Documentation: Creates a formal record of the problem and the steps taken to address it.
• Corrective Action: Provides clear, actionable steps for the recipient to take to resolve the issue.
• Consequences: Warns of potential repercussions if the behavior or violation is not corrected.
An FDA 483, formally the Notice of Inspectional Observations, is a document issued by the U.S. Food and Drug Administration (FDA) to companies after an inspection to detail conditions or practices that may violate the Food, Drug, and Cosmetic Act (FD&C Act) or other regulations. It serves as a formal notification from the investigator to the inspected company’s management about potential issues, but it is not a final determination of noncompliance. Companies are expected to provide a response to the observations, outlining their corrective actions to bring the facility into compliance.
According to FDA data, 3,344 observations were written to pharmaceutical firms in 2024. However, the best time to stay in compliance with cGMP for quality is before you feel the consequences of a failing inspection. The best way to ensure you don’t get a 483 is to focus on the 7 most common and likely areas and compliance issues that cause them and how you can handle them.
Challenges in pharmaceutical Quality Assurance (QA)
stringent and evolving global regulations, complex supply chains, ensuring data integrity in digital systems, attracting and retaining skilled talent, the transition from manual to digital/automated processes, communication gaps between departments, and pressure to control costs while maintaining high quality and compliance standards.