Change Control in FDA and ISO Environments
Tags: Regulatory Compliance, Regulation, Iso, Compliance, FDA

For Life Sciences 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 with life sciences and other regulated industries, where manufacturers must contend not only with cutthroat competition and a dynamic market, but also stringent regulatory and International Organization for Standardization (ISO) quality requirements. Keeping up with those requirements means that life sciences companies have to strictly control and manage any changes to their processes. Not doing so could affect the safety and reliability of products and directly impact public health and safety.

Definition of Change

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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 such as standard operating procedures (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. If handled improperly, any type of change can have serious repercussions.

In the summer of 2018, the U.S. Food and Drug Administration (FDA) announced a voluntary recall of a single-use resuscitation device produced by Vyaire Medical, Inc. Vyaire recalled the resuscitation device due to a manufacturing error which may cause extra plastic material in the oxygen output connection that reduces or blocks the flow of oxygen to the patient. The FDA noted than an undeclared change to the manufacturing process of the resuscitation device likely led to this production error. Whether it’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 9000:2015 and ISO 13485:2016 standards are required to ensure that any changes affecting the quality management system (including product requirements, design, and development changes) are controlled.

The underlying message in these regulations is that all changes should be made according to approved 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 highly regulated 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 may or may not be in charge of implementing the change. 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 one for 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.

Challenges

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 poor communication, poor turnaround, ineffective documentation, and training not being integrated with change are among the most common problems. If the deviation or a new step is not documented properly in the master production record and taken through a change control process, the deviation can occur over and over, causing delays and possible product recalls.

Conclusion

The internet has made consumers worldwide more aware of 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.

Jason Clegg is MasterControl’s director of marketing strategy. His experience covers more than 20 years of marketing, from traditional paper-based campaigns to digital media. Clegg has directed MasterControl’s marketing growth from a small document control company to an international provider of quality management solutions.