Regulatory Beat: Biotech Firms Face New GMP Policies

FDA is considering rule changes as it implements the second phase of its GMP modernization initiative.
Nov 01, 2004
Volume 17, Issue 11

Over the past two years, FDA officials have issued numerous guidances and revised compliance programs as part of an initiative to revise current good manufacturing practices (cGMPs) to fit the 21st century. The agency aims to encourage manufacturers to adopt new production technologies and quality-based systems and promote risk-based management approaches for industry and within FDA itself.

Jill Wechsler
A final report issued in September summarizes FDA's accomplishments during the initial assessment phase of this initiative. This 30-page white paper describes how quality systems and risk-based approaches can enhance FDA plant inspections, application reviews, post-approval changes, and electronic submissions. It also discusses how these initiatives should encourage manufacturers to implement process analytical technology (PAT) and continuous manufacturing improvement to reduce product variability. The report sets the stage for "shifting from assessment to implementation," explained David Horowitz, director of CDER's Office of Compliance, at the PDA/FDA conference in September.

A new draft guidance on how drug and biotech manufacturers can establish comprehensive quality systems approaches to comply with GMP regulations and international standards is a cornerstone of the initiative. The proposal outlines the elements of a robust quality system, including management responsibilities and resources as well as manufacturing operations and evaluation activities. It links recommendations for building quality systems to specific GMP provisions, indicating where and how the regulations fit within the model and where they may diverge. For example, the guidance notes that GMP regulations require a higher standard for equipment calibration and maintenance than most quality system models and place more emphasis on process and testing equipment.

HARMONIZING REGULATIONS Industry comments on this draft proposal will help FDA decide whether and how it needs to revise basic GMP regulations, always a lengthy and arduous task. Last year, FDA officials agreed it was necessary to change the regulations governing electronic records and signatures (21 CFR Part 11), which have generated complaints and confusion among manufacturers for years. Now agency officials indicate that it may be necessary to modify certain GMP regulations (21 CFR, parts 210 and 211) to reflect a risk-based regulatory approach. FDA wants to harmonize differing manufacturing policies for drugs and biologics with those for medical devices to simplify oversight of the increasing number of combination products.

This decision to open the door to new rulemaking emerged from a year-long analytical exercise to determine what it would take to bring all FDA regulated medical products "under one umbrella cGMP regulation," explained Kimberly Trautman, medical officer in the Center for Devices and Radiological Health (CDRH), at the PDA/FDA conference. The GMP Harmonization Analysis Working Group was established in July 2003 to compare existing regulations and assess the value of making rule changes. After comparing GMP regulations for all FDA product areas and examining differences and similarities between US and EU standards, FDA officials decided to modify current rules.

The September report notes that the working group found more similarities than differences among various GMP regulations and that FDA will take "an incremental approach" to modifying the rules. If necessary, new rule-making will be launched to clarify regulations, further international and internal harmonization of manufacturing requirements, and improve FDA's ability to detect product defects and quality problems.

As a first step, FDA is withdrawing a 1996 proposed rule that sought to update GMP requirements for process and methods validation by clarifying quality control and documentation requirements. The proposal generated 1,500 comments and was put on hold. FDA says it will take a "fresh look" at those comments along with industry responses to the new quality systems draft guidance. Another indication of the need to revise regulations may come from comments to a new draft guidance on GMPs for combination products that aims to allow manufacturers of combination products to follow only one GMP policy.

Any revision in GMP regulations will seek to harmonize US rules with standards in Europe and other nations. FDA is pursuing collaborative efforts through the International Conference on Harmonization (ICH), which is working on proposals (Q8, Q9) to establish a common approach to pharmaceutical quality systems based on risk management. FDA also announced in September that it will join the Pharmaceutical Inspection Cooperation Scheme (PIC/S), a cooperative arrangement among international health authorities to harmonize cGMP standards and quality pharmaceutical inspection systems.

lorem ipsum