The issue of pharmaceutical compounding may have dominated much of 2012 and the first half of 2013, but regulators have released few Warning Letters to compounding pharmacies in almost a year, and none since a new trio of compounding guidances came out in December 2013. Now the agency has released its first Warning Letter to a compounding pharmacy in six months, reflecting new authorities and old problems.

The 14 January 2014 letter to Triangle Compounding Pharmacy comes after a February and March 2013 inspection of the company's Cary, NC, facility. The company reportedly compounds sterile drug products, and had already been the subject of a March 2013 FDA Form 483 outlining alleged deficiencies identified at the manufacturing facility after that same inspection.

503A Violations

While there, FDA inspectors said they determined that the company was not receiving valid prescriptions for individually-identifiable patients-a violation of Section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act). Regulators said that despite "conflicting judicial decisions regarding the applicability of Section 503A" at the time of the inspection, the relevant sections of 503A and the agency's own Compliance Policy Guidance (460.200) were both applicable and in effect.

"During the FDA inspection, investigators observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce," FDA wrote. "Based on this factor alone, those drugs were not entitled to the statutory exemptions for compounded drugs described in section 503A of the FDCA and did not qualify for the agency's exercise of enforcement discretion set forth in the CPG."

FDA also noted that since the inspection, Congress and the president enacted the Drug Quality and Security Act (DQSA), which affirmed that the 503A restrictions against compounding products without a valid prescription are "applicable in every federal judicial circuit."

FDA also explained those authorities at length in a trio of guidance documents released in December 2013, and the Warning Letter-in addition to another released on the same day--appears to be the first instance of FDA expressing those authorities.

Sterility Concerns

But even outside of the above complaints, FDA maintained that Triangle Compounding has more serious problems related to the sterility of its products.

"FDA investigators noted that your sterile drug products were prepared, packed, or held under unsanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health," the agency wrote in its Warning Letter.

Those allegations were backed by a number of observations. In one alleged case, an employee was observed to be leaning against a manufacturing hood, causing it to "shake while aseptically filling syringes."

In another case, a failed test result intended to assess sterility was invalidated "without an appropriate basis." In other cases, investigators found sterile manufacturing hoods located next to "large windows with blinds"-a difficult surface to clean-and walls that were neither smooth, flat nor readily cleanable.

In general, FDA added, the company exhibited a number of more general practices that failed to meet current good manufacturing practices (CGMPs) as well, such as following written testing procedures or investigating batch failures.

The company was ordered by FDA to remedy all alleged deficiencies within 15 days of receipt of the letter, and was advised to bring in a third-party consultant to conduct a comprehensive evaluation of its systems and procedures.