Medical Device Link.

Originally Published PMPN November 2003

REGULATORY FOCUS

Daphne Allen

FDA has announced progress toward modernizing its good manufacturing practices (GMPs) for pharmaceuticals, an effort announced a little more than one year ago. In a conference call with the media in September, Commissioner Mark B. McClellan restated the agency’s objectives, which include fostering “more precise and effective medicines that are safe and that get to the patient efficiently.” To that end, the agency is “encouraging innovation” and “enhancing the consistency of regulatory programs and policies,” he said. The progress represents the effort of 16 multidisciplinary groups. McClellan was joined by nearly a dozen other agency representatives during the conference call.

While the agency effort is broad, much of the work will influence drug packaging. For instance, three of the five guidances recognized during the conference call relate to packaging. These include: 

• Guidance for FDA-regulated industry on the use of electronic records and signatures.
• Draft guidance on the aseptic processes used in the manufacture of sterile drugs.
• Draft guidance for process analytical technology (PAT).

Joseph Famulare, director of CDER’s Division of Manufacturing and Product Quality, Office of Compliance, said that all previously issued 21 CFR Part 11 guidances have been withdrawn and will not be reissued. A scope and applications guidance issued in August 2003 states that FDA “will narrowly interpret the scope of part 11. While the reexamination of part 11 is under way, we intend to exercise enforcement discretion with respect to certain part 11 requirements. That is, we do not intend to take enforcement action to enforce compliance with the validation, audit trail, record retention, and record copying requirements of part 11 as explained in this guidance. However, records must still be maintained or submitted in accordance with the underlying predicate rules, and the agency can take regulatory action for noncompliance.”

During the conference call, Famulare explained that FDA “will announce rulemaking in the future and bring in public comment.”

Regarding FDA’s aseptic processing guidance, Robert Sausville, branch chief of CBER’s Division of Case Management, Office of Compliance, said that the draft guidance covers new ground. “Science has evolved since the 1987 guidance, so the new guidance includes several new topics, including personnel, isolator technology, blow-fill-seal processes, and rapid-test methods for identifying microbes.” Sausville called isolator technology a “very encouraging process,” and he said that the role of personnel is a “critical” one. 

PAT is defined by FDA as “a framework for allowing regulatory processes to more readily adopt state-of-the-art technological advances in drug development, production, and quality assurance.” Douglas Ellsworth, district director of the Office of Regulatory Affairs’ New Jersey District, explained that FDA will collaborate to use PAT in three of FDA’s centers: CDER, CVM, and ORA. CBER will be joining that collaboration at some future point.

“We will expand inspectional PAT to cover pharmaceutical manufacturing lines and inspectional policies for quality lines,” Ellsworth said. 

In addition to working on these three guidances, FDA has begun improving its internal processes. For instance, the agency has set up the Pharmaceutical Inspectorate (PI), which will be made up of a staff within FDA’s field force of “highly trained individuals who will devote most of their time to conducting human-drug- manufacturing quality inspections on the majority of prescription drug manufacturers and other complex or high-risk pharmaceutical operations.” 

FDA is also supporting global harmonization of international drug standards. According to the agency, several scientific workshops are planned overseas in late 2003 and early 2004 “to educate, discuss, and identify innovative scientific approaches to achieve several goals of the Pharmaceutical cGMPs for the 21st Century Initiative.”

McClellan said that FDA’s work in modernizing drug GMPs ties in with the agency’s Five-Part Plan, an effort to educate patients on FDA-regulated products and protect them from the risks associated with using those products. Both efforts “involve the widespread use of efficient risk management,” he said. “Quality improvement is an on-going process.”

For more information on FDA’s initiative, visit www.fda.gov/cder/gmp/index.htm.  

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