Repeat offenses prompt FDA to revise aseptic processing guideline
By Tammy Wright
Newport, RI — Repeat deficiencies in current Good Manufacturing Practices (cGMP) are fueling the Food and Drug Administration`s efforts to revise its guideline on sterile drug products produced by aseptic processing. The most common deficiencies identified in 1997 involved lab controls, records and process controls.
The guideline was originally published in 1987 as a non-legal means of helping companies comply with certain sections of cGMP regulations for drug products (Title 21 Code of Federal Regulations, Parts 210 and 211). A working group at FDA`s Center for Drug Evaluation and Research began updating the document in July 1997 in response to advances in technology and omitted issues, such as personnel practices. However, trends emerging from field observations and investigations reflect the need for an immediate call to action from the agency.
“We had comparable deficiencies in 1996 and 1997, and we have the same outstanding issues in 1998,” Joyce E. Bloomfield, FDA compliance officer/sterile products, told more than 100 session attendees at the GMP by the Sea Bio pharma ceutical/ pharmaceutical Con fer ence held in September in Newport, RI. “Trends of repeat observations give us the basis for changing guidance.” (At press time, Ms. bloomfield had resigned from the FDA to accept a compliance consultancy position with KMI/Parexel.)
For example, Bloomfield says a primary concern noted on 483 observations regarding lab controls was the use of unvalidated test methods.
Another area of concern involved retests conducted without appropriate investigation. FDA staff chemist Russ Rutledge says companies must cite reasons for retesting and the results must demonstrate why errors occurred and how they`ve been corrected.
“We have a real problem with companies that throw away (failing) test results until they get a passing sample,” Rutledge explains. “A company has to find out what`s making its product out of specification.”
To address the issue of retesting, the FDA has written a draft guideline entitled, “Guidance for Industry: Investigation of Out-of-Specification Test Results for Pharmaceutical Products.” The document is currently pending release for public comment.
While administration officials aren`t outlining specifics to be included in the revised guidance at this time, they claim all major topics in the current version are being updated, with new sections to be added on personnel, cleanroom design, endotoxin control, pre-filtration bioburden testing, batch record documentation, and barrier isolator technology.
Bloomfield says two issues receiving significant attention are cleanroom design and personnel training and practices.
Cleanroom design, she contends, weighs heavily in preventing the microbiological contamination of products purported to be sterile. “Factors to be considered are types of surfaces used and how easy they are to clean; the flow of personnel and materials in and out of the room; the use of HEPA-filtered air; and the size and location of equipment in the room.
“The revised guidance also explains the importance of aseptic processing technique, gowning qualification and the need for written training programs and established procedures,” Bloomfield says, citing her own observations of poor employee habits like exposed skin in the manufacturing area or failing to sanitize hands. “These issues are critical because personnel practices can have a direct impact on product sterility.”
This expanded guidance on personnel issues will be beneficial to industry, according to Jeffrey T. Yuen, a former California State and FDA field investigator and president of Jeff Yuen and As sociates, a quality and validation consultancy com pany (Orange, CA).
He believes most firms follow GMPs in spirit, but says the human factor is the greatest variable, and therefore, the most critical part of production control.
“I`ve always been a proponent of controlling things and minimizing bioburden. To the extent to which people are involved, the (revised) guideline should carry a degree of importance,” adds Yuen.
Bloomfield says the target date for public release has been set for sometime in 1999. CR