What does the FDA expect from your contamination control procedures?
Next month, the FDA`s Quality System Regulations go into effect. Originally established in 1978 as good manufacturing practices (GMPs), they were renamed and differ significantly from their predecessor.
By Lisa A. Karter, Chief Editor
In October 1996, the FDA announced its new standards for medium and high risk medical devices. The changes were designed to make the devices safer and more effective and also to align the United States with emerging worldwide
regulatory requirements. The FDA estimates the biggest benefit of the new standards will be the prevention of 36 to 44 deaths and 484 to 677 serious injuries annually, with the medical device industry picking up the $81.9 million cost of implementation.
“To achieve these benefits, medical device manufacturers must now incorporate a set of checks and balances in their design processes to assure a safe, effective finished product,” says FDA spokeswoman Sharon Snider. The new standards, renamed Quality System Regulations (QSRs) — a revision of GMPs — go into effect in June. But, to give industry enough time to make the transition, FDA will not enforce the design control provision (Sec. 820.30) until after June 1998 — when equivalent design controls will become mandatory in Europe.
The new standards follow the International Organization for Standardization`s ISO 9001, and fulfill a mandate of the Safe Medical Devices Act of 1990 to harmonize these requirements. The new QSR incorporates changes suggested by the medical device industry in response to a proposed rule FDA published in November 1993 and a working draft published in July 1995. The changes, which were endorsed by FDA`s GMP Advisory Committee in September 1995, give manufacturers greater flexibility in achieving quality requirements. The new regulation describes the objectives of each control tool but allows manufacturers to develop their own methods for implementing them.
The most important change in the new regulations is the addition of design control requirements. The FDA found that approximately 44 percent of quality problems that led to voluntary recall actions between 1983 and 1989 were due to error or deficiencies that had been designed into particular devices and may have been prevented by adequate design controls.
Your quality system
The new regulations will require manufacturers to extend their quality systems to include several new areas — such as design and purchasing — and to clarify and expand selected existing requirements. Several of the changes make the regulation more consistent with ISO 9001:1994 quality standards. According to the FDA, the rules will affect all medical establishments engaged in designing, manufacturing, contract sterilizing, and packaging medical devices.
According to Lireka P. Joseph, the director of the Office of Health and Industry Programs at the Center for Devices and Radiological Health, an arm of the FDA, “the Quality System regulation outlines the minimum elements of a system for designing and producing a medical device.”
Because the regulation must apply to so many different types of devices, it cannot prescribe in detail how a manufacturer must produce a specific device. “Rather, the regulation provides the framework that all manufacturers must follow by requiring that manufacturers develop and follow procedures and fill in the details that are appropriate to a given device according to the current state-of-the-art manufacturing for that specific device,” says the FDA.
Even if your company is certified to ISO 9001:1994, that may not be enough. Although the FDA did adopt language from ISO 9001, it did not adopt ISO 9001:1994 verbatim for two reasons: First, there were complications in dealing with the issue of copyrights; and second, “FDA, along with health agencies of other governments, does not believe that for medical devices, ISO 9001:1994 alone is sufficient to adequately protect the public health,” states the FDA`s cGMP Final Rule document.
What`s new for contamination control?
One thing that has not changed in the new FDA QSRs is that there is still no requirement for a cleanroom in medical device manufacturing. The FDA`s newest Quality Systems Manual does specify that the buildings and environments in which components, devices and records are received, processed, built and stored “should be controlled.” It also says that the degree of control “should allow for appropriate changes in such elements as temperature, humidity, bioburden, particles, personnel, components, devices and records.”
Environmental contamination and insufficient space are the most typical problems in receiving and holding incoming products prior to testing and inspection [820.70(c); 820.70(e); and 820.70(f)]. The Quality System Manual specifies that: “for each area in the building where products are processed, any elements such as particulate from cardboard dust, by-products from slitting or cutting operations, microorganisms, humidity, temperature, static electricity, etc., which a manufacturer has determined might cause contamination should be controlled.” The FDA also recommends that buildings should be constructed to prevent such contamination.
While the FDA hints at controlled environments, the QS Manual actually recommends Federal Standard 209E as a guideline for establishing parameters for temperature, humidity, colony-forming units and particulate per cubic foot.
Section 820.70(e) requires that “each manufacturer establish and maintain procedures to prevent contamination of equipment and product by substances that could reasonably be expected to have an adverse effect on product quality.” The QS Manual also says these procedures should be established by the manufacturer to ensure its products meet its quality claims, for example, in vitro devices that are not contaminated with microbes, detergents or rodenticides. Manufacturers should either “carefully control” the environment in which such devices are manufactured and processed to minimize contamination with bacteria or establish a procedure for cleaning the devices.
Contamination control procedures
Although strict contamination control procedures are not outlined in the new QSR, the QS Manual gives examples of procedures that may be used to comply with the cleaning or contamination control requirements set out in the QS regulation.
Some of the general requirements highlighted include the following:
No eating, drinking, smoking or chewing gum.
Wear specified garments both when entering and working inside the clean area. Garments should be stored in the anteroom and not worn in non-clean areas.
Use only approved cleanroom paper in the clean area.
Use only ball-point pens (fine point preferred).
Also included are cleaning procedures for aseptic filling rooms: control of surface contamination within an aseptic filling area and daily and weekly cleaning requirements. [Much more detail can be obtained on the World Wide Web at http:// www.fda.gov/cdrh/qsr/06bldng.htm].
What the FDA doesn`t like
According to the QS Manual, FDA investigators conducting factory inspections do not like to see improperly trained employees working in medical device manufacturing facilities. FDA investigators also object to employees smoking near or sweeping dust into open processing tanks (smoke and dust would destroy the usefulness of the device) blowing smoke or sweeping dust onto devices to be sterilized; handling delicate devices while wearing rings and other pieces of jewelry; wearing gloves with holes, etc.
According to the QS Manual, such employee practices cause FDA inspectors to ask whether management is reminding employees why they are not allowed to do certain activities. In section 820.25, the QSR requires that “each manufacturer shall have sufficient personnel with the necessary education, background, training, and experience to assure that all activities required by this part [820.35] are correctly performed.”
In addition, the QSR mandates that: “each manufacturer establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, and this training is to be documented. The QS Manual recommends that new employees be “initially trained” to perform their specific jobs and made aware of the defects that can occur from bad performance and contamination, such as poor hygiene, poor health, smoking or eating on the job, and “other detrimental factors.”
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Cleanroom personnel at Medrad, Inc. (Indianola, PA) are manufacturing tubing used in various medical devices. Photo courtesy of Clestra Cleanroom, Inc.