FDA/ISPE guidelines ease regulatory burdens
By Sheila Galatowitsch
Tampa, FL — Pharmaceutical manufacturers can now make immediate post-approval equipment changes, thanks to new FDA guidelines that minimize the red tape. The guidelines make it easier to identify filing requirements for equipment changeouts and minimize the amount of regulatory data that needs to be generated. In many cases, pre-approval review for equipment changes may not even be necessary.
The equipment guidelines are addenda to Scale-Up and Post-Approval Changes (SUPAC) — the most significant piece of industry guidance from the FDA in years (see related story, page 48), says Dr. Russ Somma, chairman of the International Society for Pharmaceutical Engineering`s (ISPE) SUPAC steering committee that helped develop the addenda. Somma is also assistant director of solid dosage forms, process development, at Novartis Pharmaceuticals Corp. (Summit, NJ).
Yet many companies, habituated to lengthy approval cycles, may find it difficult to embrace the freedom that SUPAC and the equipment guidelines offer, Somma says.
To get the benefits of the regulatory relief, companies should form a consensus on certain unit operations and the way data validation packages are constructed to ensure that “a good solid developmental history” will support changes made, Somma says. Companies will still be regulated under SUPAC and the addenda, so stability programs and validation packages must be capable of withstanding investigation and scrutiny.
Abbott Laboratories (Chicago, IL) has already changed its internal documents to reflect the same terminology used in the guidelines, says Richard Poska, senior regulatory affairs scientist and a member of the ISPE SUPAC steering committee. Consistency between the FDA guidelines and internal documents will make inspections easier, Poska says.
The company has also used the equipment addenda to make changes and determine filing requirements associated with the changes. “Speed is where the industry is gaining the monetary benefit of SUPAC,” Poska says.
But in certain cases, companies may be better off making traditional formal appeals for changes, he says. To determine when SUPAC will benefit a company, regulatory personnel, as well as technical operations and development personnel, should have a clear understanding of the guidance documents.
Douglas Sporn, director of the FDA`s Office of Generic Drugs, advises manufacturers to get as much exposure to the guidances as possible, through web site information (www.fda.gov/cder) and trade associations. “And it would be helpful to have at least one person in an organization familiar enough with the guidances so that when a post-approval change needs to be made, the guidance can be checked to see if it makes filing requirements simpler and faster,” Sporn says.
The addenda make equipment changes easier by defining SUPAC`s reference to equipment with “similar design and operating principles.” They group equipment into classes and provide lists of comparable equipment in common use within the industry.
“The equipment addenda render a glossary or lexicon so that industry speaks the same language and has a level playing field,” Somma says. “The identification by class is key. If you stay within a class and subclass, you are defined as having the same design and operating principle.”
If companies are changing out comparable pieces of equipment as listed in the equipment addenda, they have only to indicate that in their annual report to the agency, Sporn says.
The uniformity of the guidance documents also makes FDA inspections and decision making easier, Sporn says. “It gives everybody the same set of marching orders in terms of how they can make judgments about when equipment is or is not the same.”
In addition to making it easier to change manufacturing equipment, SUPAC is also “a boon to third-party manufacturing and a boon to outsourcing, ” Somma says. “The utility of SUPAC is limited only by the imagination of the companies using it.”
Deploying SUPAC early in product development can help companies “lay out a strategy to leverage change in a heavily regulated environment. It will make companies more successful,” Somma says. Building in SUPAC as part of a new drug approval, especially for global products, gives companies more flexibility in making site transfers and process improvements, and installing new equipment without prior FDA approval.
In fact, the biggest use of SUPAC thus far has been for site changes, says Sporn. CR
SUPAC and equipment guidance addenda
The Guidances for Industry for Scale-Up and Post-Approval Changes (SUPAC) were developed by the FDA`s Center for Drug Evaluation and Research (CDER) with the goal of reducing regulatory burden on industry.
They cover post-approval changes for components and composition, equipment, site and process; and outline information that should be provided to CDER to assure continuing product quality and performance characteristics when post-approval changes are made.
Each SUPAC guidance addresses a specific dosage form, such as immediate release tablets and capsules. Three of the proposed six documents are available for industry use and can be viewed on CDER`s web site (www.fda.gov/cder). They include SUPAC Immediate Release Solid Oral Dosage Forms (SUPAC-IR); SUPAC Modified Release Solid Oral Dosage Forms (SUPAC- MR); and SUPAC Semi-Solid Topical Dosage Forms (SUPAC-SS).
For each SUPAC document there is or will be a corresponding equipment guidance addendum developed jointly by equipment experts at the ISPE and the FDA. The addendum for SUPAC-IR is also on the CDER web site. The addendum for SUPAC-SS has been drafted by ISPE and is under FDA review. Still to come are SUPACs and equipment addenda for transdermal systems, bulk actives and sterile aqueous solutions. — SG