FDA’s High Risk Pharmacy Inspections and Enforcement Actions: Coming to a Sterile Compounding Pharmacy Near You?

By Karla L. Palmer & Jeffrey N. Gibbs –

On Thursday, April 11, 2013, FDA published a statement titled, “2013 FDA Pharmacy Inspection Assignment,” addressing the unprecedented recent nationwide wave of aseptic pharmacy inspections.  The Agency states that it had taken critical look at its surveillance and enforcement approach to pharmacies that “produce” sterile drug products.  The objective of FDA’s pharmacy inspection assignment was to determine whether certain pharmacies that produced high-risk sterile drug products in the past “posed a significant threat to public health from poor sterile production practices.”  FDA developed a risk-based model when choosing the 29 pharmacies for the priority inspections.  According to FDA, the risk criteria included consideration of serious adverse event reports, historical inspection data, and reports of product quality problems.  FDA did not disclose from what sources it obtained information on the particular pharmacies at issue and how it applied that information to select the 29 pharmacies that made the inspection list. However, FDA said it targeted for inspection pharmacies that met at least two of three of the risk criteria or had a reported death from their products.   

The FDA’s inspections took place over a seven-week period from February to April 2013.  As of April 11, 2013, FDA completed 29 of 31 inspections (it identified two additional entities associated with the initial priority group that it still needs to inspect).  Ninety percent of the inspections (28 out of 31) were conducted in cooperation with state boards of pharmacy or other state officials, and occurred across 18 different states.  The FDA claims it mobilized “highly-skilled, certified drug investigators who have specialized experience and specific training to evaluate pharmaceutical production and determine a firm’s compliance with sterile production standards.”  FDA states that the inspectors interviewed the pharmacy’s technicians, and collected information on operations, standard operating procedures, and products in order to learn more about the firm’s sterilization methods and drug stability program.  “The inspectors also reviewed the firm’s potency, sterility and endotoxin failures, as well as the firm’s air flow studies (if present).  If warranted, investigators collected samples when they observed an abnormality, such as drug product residues, particulates or discoloration within the production environment or the actual sterile drug product.”  The FDA inspectors evaluated the pharmacies “according to federal standards regarding aseptic practices,” which we assume means federal current good manufacturing practice (“cGMP”) (21 C.F.R. Parts 210 & 211), to which drug manufacturers and not state-regulated compounding pharmacies are held.  Several pharmacies apparently put up some resistance to FDA’s assertion of broad inspection authority.  Some required FDA to obtain administrative warrants or otherwise initially refused FDA access to their facilities.  Either through administrative process or consent, however, the pharmacies ultimately permitted FDA to inspect the facilities.

Of the 29 completed pharmacy inspections, FDA has issued observations (FDA Form 483s) to all but one pharmacy.  FDA notes that select Form 483 observations during the inspections include: “incomplete and/or inadequate drug product batch failure investigations, inappropriate and/or inadequate clothing for sterile processing, lack of appropriate air filtration systems, insufficient microbiological testing,” and other “practices” that FDA believes “create a risked of contamination.”  These observations appear to be based on applying cGMP requirements to compounding pharmacies.  FDA’s report does seem to assume that all observations are accurate and appropriate, even without waiting for responses from the pharmacies.

As “next steps” concerning its enforcement activities against these and other pharmacies, FDA states that it is currently evaluating information obtained during inspections and will exercise its “existing legal authority to protect the public health.”  The FDA notes that, for pharmacies that are operating outside the yet-to-be-defined “bounds of traditional pharmacy compounding and who had significant production issues,” it intends to “take aggressive action, including through enforcement actions.”  However, the Agency does admit that it “may not be able to take enforcement action against firms that meet certain criteria and are operating within the bounds of traditional pharmacy compounding, unless certain provisions of the law are violated, such as producing or distributing a contaminated drug product.”  This acknowledgement of the limits of FDA authority did not preclude FDA from issuing Form 483 notices of observations based on cGMPs. 

The question of FDA’s role in regulating compounding is the focus of increased attention.  Legislation is being considered to give FDA greater authority over compounding pharmacies.  On April 16th, the House Committee on Energy and Commerce will hold a hearing regarding FDA’s handling of NECC.  The release by FDA of its report on new inspections may, perhaps, be cited by FDA at this upcoming hearing to show that FDA is taking an active role in this arena.