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A direct response to the devastating fungal meningitis outbreak linked to NECC, the Drug Quality and Security Act gives FDA needed regulatory power to oversee compounders.
Sometimes it takes a significant crisis to forge the adoption of appropriate government regulations. Passed last November, the Drug Quality and Security Act (DQSA) is a direct response to the aftermath of the devastating fungal meningitis outbreak linked to the New England Compounding Center (NECC). The legislation, intended to regulate compounding pharmacies and establish a track-and-trace pedigree system for drugs, has engendered a sigh of relief in some patient-safety circles.
Christopher J. Topoleski“The NECC catastrophe highlighted dangers of unregulated, large-scale compounding,” said Christopher J. Topoleski, BA, director of Federal Regulatory Affairs at the American Society of Health-System Pharmacists (ASHP), Bethesda, Md.
After a federal investigation of outsourcing facilities, the FDA and Congress determined that poor regulatory coordination and gaps in pharmacy oversight may have contributed, in part, to the fungal meningitis outbreak.
For decades, the FDA has had authority to regulate drug manufacture, but the compounding of “designer therapeutics” falls into a gray area between state and federal oversight.
Critics of the previous system assert that the optimal way to balance the need for custom medications with the need for product safety is to give FDA broader powers to regulate compounders.
David G. MillerExcept for removal of advertising prohibitions, section 503A of the new legislation is essentially unchanged and “applies to all licensed physicians and pharmacists who are engaged in compounding or who compound for individual patients based upon a valid prescription,” said David G. Miller, RPh, executive vice president and CEO, International Academy of Compounding Pharmacists (IACP) in Alexandria, Va.
In this case, the standards are clear. The pharmacist can use only drugs that: are part of an accepted nationwide standard, have not been withdrawn or removed from the market for safety or efficacy reasons, are not on a “demonstrably difficult” to compound list, and are not “copies” of commercially available products.
Topoleski said that ASHP is asking FDA for further guidance, such as an unambiguous definition of “demonstrably difficult” and an updated drug products list to replace the current one, which was created 15 years ago. Miller noted that “future handling of homeopathic products, dietary supplements, and OTC products still remains unknown.”
Pharmacies that ship products across state lines must operate in a state that has signed a memorandum of understanding (MOU) with FDA. In the absence of such an agreement, they can distribute no more than 5% of the total prescription orders to another state.
Miller believes that the new legislation has not really changed compounding practices for traditional compounders, but it has raised some unanswered questions about what practitioners are to do in day-to-day patient care when current state and federal laws appear to conflict or when prescribers do not understand or believe that this law applies to them as well. “Doing the ‘right’ thing for the patient may actually conflict with the law,” he said.
The establishment of the new “outsourcing facility” 503B category creates the opportunity for custom sterile drug compounders to voluntarily register with the FDA.
Topoleski considers the new law a pathway for increased patient safety and information transparency; it will help ensure that compounding entities are compliant with current good manufacturing practices (cGMP) requirements and are subject to routine and risk-based FDA inspections, much as are drug manufacturers.
“A 503B outsourcing facility must report which products they are compounding and any associated adverse events,” said Topoleski.
Under the new bill, outsourcing facilities are also not allowed to compound copies of drugs already on the market, unless they are on a drug shortage list. In that event, the compounder must follow new labeling requirements.
In Topoleski’s view, lack of state and government resources, as well as funds available for policing sterile compounding facilities, has long been a challenge.
The recently published FDA draft guidance “for industry on Section 503B fees for drug compounding outsourcing facilities” may help alleviate the problem (available at www.fda.gov). This draft guidance sets forth FDA’s thinking on annual establishment and reinspection fees, as well as procedures for submitting payment and annual fee adjustments. Starting in 2015, outsourcing facilities must pay the FDA an annual $15,000 fee.
Supporters of the regulation acknowledge that a voluntary approach will succeed only if prescribers and hospitals choose to align with FDA-registered outsourcing facilities. Safety advocates are concerned that the legislation leaves the door open to more rogue pharmacies that may continue to place patients in harm’s way.
Rachael G. PontikesAccording to Rachael G. Pontikes, partner, Duane Morris LLP in Chicago, Ill, the new legislation encourages enhanced communication between FDA and state boards of pharmacy.
The state boards will continue to regulate the practice of pharmacy, including traditional pharmacy compounding. However, state boards will now be required to report disciplinary actions taken against a pharmacy for compounding violations or those taken against a compounding pharmacy for other violations, which may prompt an FDA inspection/determination.
One of the root causes of the NECC tragedy was gaps in inter-organizational communication. There was poor communication between FDA and individual state boards of pharmacy and among state boards of pharmacy in various states, Pontikes said.
“My company, PharMEDium, has been an advocate for the new law and was the first entity to voluntarily register with the FDA in the newly created outsourcing facility category,” said Rich Kruzynski, RPh, MBA, president of PharMEDium Services, Lake Forest, Ill, in a recently published opinion piece.
While DQSA has certainly affected PharMEDium, many of the requirements for outsourcing facilities are not new to the company; it has been registered with FDA and undergone FDA inspection since its inception more than a decade ago.
Kruzynski noted that the new legislation has called for one significant labeling change. All products, including IV containers or their packaging, must include the following text: “This is a compounded drug.” He said that his company is exploring ways to ensure a uniform visible representation of this requirement, which will help ensure safety and transparency in the medication administration process. The company has also added DQSA-required phrases to its labeling - “Not for resale” and “Hospital/Office use only” - and incorporated FDA’s Adverse Event Reporting website and phone number.
As of mid-April, of the estimated 3,000 compounding pharmacies that make sterile injectable drugs, only 38 had registered as 503B outsourcing facilities, of which 16 had been inspected. (For a complete list, go to www.fda.gov). The most striking finding is that all the inspected facilities were issued Form 483, which describes significant “objectionable conditions” observed by the investigators.
While some observers take encouragement from the fact that FDA is aggressively inspecting and citing facilities for potential deviations from cGMP, how many compounders will ultimately register remains to be seen. Even with the new law in place, significant questions remain, concerning the regulation of facilities that do not register with FDA, yet still perform outsourcing.
Miller acknowledges that enactment of the DQSA has helped pharmacy to focus on the importance of compliance and practice standards. He urges pharmacists to pay attention to - and comment on - regulations at both the state and federal levels, so that “the government makes informed decisions that do not affect proper medication management and patient care.”
Even with the new legislation in place, it will be up to prescribers to determine which compounding pharmacies to employ.
“When making this selection, use a checklist,” Miller said, and make sure it includes these questions: Is the pharmacy appropriately licensed? Have there been any disciplinary actions?
Monica Shah, PharmD, is a hospital pharmacist and healthcare journalist based in Iselin, N.J.
Keeping it in-house Drug Topics June 2014