Change Control - Continuous Quality Improvement in FDA and ISO Environments

For Life Science Companies

Globalization of the marketplace has greatly intensified competition and has increased the pressure on manufacturers to develop innovative, high-quality products faster and at a lower cost. To stay competitive, manufacturers must be quick to meet customer demands and even quicker in adapting to changing market conditions.

The situation could not be more acute than in the FDA and ISO environments, where manufacturers must contend not only with cutthroat competition and a dynamic market, but also stringent regulatory requirements. Consider the fiercely competitive pharmaceutical industry. Only one of every 10,000 potential medicines investigated by American research-based pharmaceutical companies survives the rigorous FDA approval process, according to the Pharmaceutical Research and Manufacturers of America. It takes about 15 years at a cost of more than $800 million before a new medicine is approved.

In this context, any change that affects the "purity" and effectiveness of the approved product is critical.
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Definition of Change

In the manufacturing environment, change refers to any modification in equipment, manufacturing materials, facilities, utilities, design, formulations, processes, packaging/labeling, computer systems, and all associated documentation (SOPs, quality manual, etc.).

A change may be a simple adjustment brought on by a new customer specification, an updated document, a part replacement, or other production need. It may be caused by a deviation from an approved regulatory filing or written procedures. A change may be temporary or permanent, routine or emergency, innocuous or serious enough to shut down production.

The fact that change is inevitable makes control a critical factor, especially in FDA and ISO-environments, where inappropriate or "uncontrolled" changes could affect the safety and reliability of products and directly impact public health and safety.

Here's an example. On October 24, 2005, the FDA announced a voluntary recall of certain models of Omron instant thermometers because the thermometer tips could potentially overheat and pose risk to young children using the device. The FDA noted that the overheating was a result of a change in the manufacturing process. The agency's press release was brief and did not describe the circumstances of the change that caused the quality problem, but it illustrates the critical implications of change in the manufacture of medical devices in this case, or any other product for that matter. Whetherit's a car or a computer or a pacemaker, the goal of regulatory bodies is to protect public safety by ensuring the highest quality standards. For this reason, the concept of change control is closely interwoven with FDA and ISO compliance.

Regulatory Requirements

Change control requirements for medical device companies are outlined in FDA's 21 CFR Part 820.30 (design changes), 820.40 (document changes), and 820.70 (production and process changes). 21 CFR Part 820 requires that manufacturers establish written change control procedures that describe company-approved procedures.

For pharmaceutical companies, written procedures are considered part of Current Good Manufacturing Practice (CGMP) outlined in 21 CFR Part 210-211. Any changes in production and processes must be controlled —meaning recorded, reviewed and approved by the quality control unit. cGMP requirements are meant to prevent harm by building quality into the development and production of medicines. Manufacturers certified to ISO 9000:2000 and ISO 13485 standards are required to ensure that any changes affecting the quality management system (including product requirements, design, and development changes) should be controlled.

The underlying message in these regulations is that all changes should be made according to approved (approval implies successful testing or thorough review/investigation) written company policies and procedures. Change control procedures have to be written as a way of standardizing instructions. Written procedures are also more reliable compared with passing on information verbally. "Uncontrolled" change in this context refers to modifications made without review and approval of the quality control unit and other departments affected by the change.

In FDA and ISO environments, strict adherence to approved policies and procedures is a key factor in keeping manufacturing operations in a state of control and it is what makes change control crucial.

Elements of Change Control

Change is typically introduced by an initiator or originator. Depending on the company and industry, the initiator mayor may not be the person who will carry the change through implementation. Initiating a change usually involves filling out a change request form, which then moves through a process or system of review and approval. Most organizations have a change control committee or board, which may be a single entity for an entire company, or there may be onefor a company's manufacturing site(s). The committee usually includes representatives from different departments involved in production, such as quality, manufacturing, regulatory affairs, and engineering. Depending on the change, the committee may also involve the legal, sales or marketing departments.

For pharmaceutical companies, the CGMP requires that all changes should be reviewed and approved by the quality control unit. In these companies, there may be a "change administrator," a role usually assumed by the quality unit.

Change control records usually cover: identification of the item/entity being changed, a description of the change, identification of the affected documents, signatures of the approvers, approval date, and effective date.

In the medical device industry, each modified device, accessory, labeling, packaging, and process must be thoroughly verified and/or validated by the appropriate department. The change control committee then reviews the test results and other pertinent information.


A change control system is necessary to prevent inappropriate modifications. While this sounds simple, implementation can be complex and an inadequate system can cause internal confusion, noncompliance, or worse, a product recall or a product liability lawsuit.

What makes change control so challenging? There are many factors, but the following are the most common issues:

  • Poor Communication - Lack of communication between departments, failure to follow up or escalate change requests and delayed or inappropriate notification of changes made by suppliers are some of the communication- related issues that impact the change control process. Companies using a paper-based change control systemare likely to rely on face-to-face exchanges, such as change control board meetings, to discuss changes. The effectiveness of these meetings depends on their frequency and the availability of members to meet as emergency changes arise.
  • Poor Turnaround - Timeliness can make or break a product's chances of succeeding in the market. Companies that rely on a manual system to generate data and to route and track submissions and change orders are likely to have poor turnaround for change implementation because the system requires more time and effort. The problem becomes worse when there is an unexpected change—a deviation—and supporting data is not generated in a timely manner. Delays may also result because of failure to recognize the urgency of a change and the absence of a contingency plan for certain types of changes.
  • Ineffective Documentation - A manual system makes it more difficult to update documentation, including revision history, and to find/retrieve necessary data to support a change. The proposed change may be delayed when an outdated record does not show revision history, or testing may be duplicated because documentation has not been updated with results of a previous testing.

  • Training not Integrated with Change - Adequate training of personnel is a prerequisite in both FDA andISO environments. When training control is not connected to the rest of the quality process, such as in manual systems, keeping training current with procedures that have changed can be difficult. Training tasks can easily fall through the cracks if employees are not vigilant in seeking them.


In this Age of the Internet, consumers worldwide have become more aware about product quality. In response, manufacturers are changing their business philosophy. Customer satisfaction and continuous improvement of product quality have become the objectives not only of regulatory bodies, but also of manufacturers themselves. At the operational level, the focus is moving from detection to prevention. Companies recognize that it's their primary responsibility to determine if a proposed change could significantly affect the safety or effectiveness of a product—and not the responsibility of the FDA inspector or ISO auditor to spot. Manufacturers increasingly realize that effective change control is integral to continuous quality improvement, which can ultimately help them increase customer satisfaction and prevent product recalls, product liability actions, and regulatory violations.