FDA Eases Phase I Manufacturing Requirements

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FDA Eases Phase I Manufacturing Requirements

On Jan.17, the US Food and Drug Administration (Rockville, MD, www.fda.gov) amended 21 CFR 210 (“Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General”) to exempt Phase I drug manufacturing from the requirements of 21 CFR 211 (“Current Good Manufacturing Practice for Finished Pharmaceuticals”) (1).

“This action,” said the Federal Register notice, “is intended to streamline and promote the drug development process while ensuring the safety and quality of the  earliest stage investigational drug products.”

The rule followed the Jan. 12 publication of the corresponding draft guidance, INDs-Approaches to Complying with CGMP during Phase 1.

The new guidance will ultimately replace the fifteen-year-old Guideline on the Preparation of Investigational New Drug Products (Human and Animal), (www.fda.gov/cder/guidance/old042fn.pdf) which required IND adherence to commercial-scale CGMP standards. In the words of the new guidance, “the 1991 document did not address fully the Agency’s expectation that an incremental approach to manufacturing controls would be taken during investigational drug development.”

The new guidance emphasizes the responsibilities of the quality control unit (lapses in which are now the leading cause of Form 483 citations) and offers some practical guidance for reducing the effort needed to comply with CGMP requirements (e.g., disposable equipment, closed or presterilized equipment, prepackaged water-for-injection, and outsourced manufacturing and analytical work.)


In the impact analysis accompanying the rule, FDA estimates that the industry spends about 848,625 person-hours per year collecting information to comply with parts 210 and 211. The new rule is expected to reduce that requirement by about 50,500 hours (6%).

“The problem is that researchers conducting very early studies were required to follow the same manufacturing procedures as those companies that mass produce products for broad scale distribution,” said FDA Deputy Commissioner for Operations Janet Woodcock in a statement that accompanied the draft guidance announcement. “These requirements are so burdensome for early Phase 1 studies that many leading medical research institutions have not been able to conduct these studies of discoveries made in their laboratories. Today, for the first time, medical researchers are getting specific advice from the FDA about how to safely prepare products for exploratory studies.”

References1. Fed. Regist.71 (10), 2458–2462, DocID: fr17ja06-4, (2006)