by Joseph X. Phillips

For a number of reasons, medically necessary drug shortages are on the increase. Last year, more than 55 shortages of medically necessary drug products occurred in the U.S. alone. Each of these shortages has the capability to significantly impact the quality of life or shorten the life of those patient groups who are dependent on the medication for treatment. A critical crisis can result when a drug supply is insufficient to treat patients who need it; one such shortage involving the influenza vaccine drew national attention in 2004, and there have been other highly visible shortages. Furthermore, drug shortages are not a new phenomenon.

The reasons for drug shortages are many:

• Bulk drug/API shortage
• Corporate decisions/mergers
• Manufacturing difficulties/compliance issues
• Market concentration/ limited production capacity/old versus new drugs
• Changes in clinical practice
• Hospital/ pharmacy based issues
• Emergency situations

The U.S. Food & Drug Administration (FDA) has been vigilant with regard to shortages, and continues to devote significant efforts to help prevent or mitigate their impact. The FDA has set up a Drug Shortage Team devoted to this issue. When the Agency learns of a drug shortage, its first action is to immediately verify that a national shortage exists. If a shortage is verified, the FDA determines if the product meets the definition of a medical necessity. The Agency defines a “medically necessary product” as one used to treat or prevent a serious disease or medical condition, for which there is no other available source of that product that is judged by medical staff to be an adequate substitute. Inconvenience alone is an insufficient basis to classify a product as a medical necessity.

If the product is identified as a medical necessity, the FDA arranges meetings among the Review Division(s), Compliance, and the drug's manufacturer to formulate short term/long term action plans to eliminate or shorten the length of the shortage or replace the drug supply. Some possible interventions include:

• Developing a protocol for limited distribution Expediting review of:
  • Pharm-tox data
  • CMC supplements
  • Alternate supply sources
  • New marketing applications (NDA/ANDA)
• Requesting company to continue manufacturing a product it plans to discontinue
• Encouraging other manufacturers to ramp up production
• Allowing temporary imports
• Employing regulatory discretion for manufacturing issues

Obviously, the Agency cannot force a manufacturer to produce a product. Manufacturers are not required to report plans to discontinue a product unless it is a sole source product for a life-supporting/life sustaining condition (See Section 506C of the FD&C Act).

FDA has requested ISPE to assist in developing new effective initiatives and to move current initiatives forward to help deal with this very critical issue. Our Board of Directors has agreed to assist in this effort, and ISPE leadership has raised the issue with our International Leadership Forum in Edinburgh, Scotland. The ILF has agreed to actively work through ISPE with the FDA. We are already developing plans for further discussion.

ISPE can use its expertise to attempt to develop new approaches, to plan educational efforts, and to assist the Agency in reaching its stakeholders.

About the Author
Joseph X. Phillips joined ISPE in 2003 as Regulatory Affairs Advisor and was appointed to the US Food and Drug Administration (FDA) as a special government employee on the Pharmaceutical Science Advisory Committee that is involved in the agency’s new “Risk-Based Approach to Pharmaceutical Current Good Manufacturing Practices (cGMPs) for the 21st Century” initiative. Previously, Phillips was Vice President, Pharmaceutical Services for Quintiles Consulting following a 44-year career with the FDA. At the FDA he served as Deputy Regional Director of the Agency’s Central Region. He was heavily involved in training of FDA Investigators and in planning and managing pharmaceutical programs including the Pre-Approval Inspection program and the SUPAC (Scale-Up and Post Approval Changes) for field operations. Phillips was a principal negotiator for the US/EU Mutual Recognition Agreement and was the FDA Lead to the International Conference on Harmonization (ICH) Expert Working Group for GMP Guidance for Active Pharmaceutical Ingredients (ICH Q7A Guidance)