There were six warning letter postings during this week: three drug warning letters including one regarding Akorn’s site in Somerset, NJ that the company announced a few weeks ago, one to a device manufacturer, one to an IRB, and one to a compounding pharmacy.

DRUGS | Akorn, Inc.

Akorn, Inc. received a warning letter dated June 13, 2019, based on the outcome of an inspection of their Somerset, NJ site ending August 30, 2018, with a 22-page form 483. The warning letter was sent to the CEO in Lake Forest, IL. FDA notes that similar CGMP violations were identified at other company facilities, noting that the firm received a warning letter in January 2019 identifying deficiencies at their site in Decatur, IL.

FDA states: “These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs are inadequate. Your executive management remains responsible for fully resolving all deficiencies and ensuring ongoing cGMP compliance. You should immediately and comprehensively assess your company’s global manufacturing operations to ensure that systems, processes, and the products you manufacture conform to FDA requirements.”

Deficiencies identified in the most recent warning letter include but are not limited to poor aseptic practices in the filling of the sterile drug product and data integrity problems. This has become the dynamic duo of almost guaranteed enforcement action. The information that FDA requests the firm provide is not going to be completed quickly.

  • The firm did not adequately investigate OOS results and manufacturing deviations to ensure they were complete and included scientifically sound conclusions and corrective actions. Many investigations were open for six months, some open for more than a year without adequate justification.
  • Adequate controls are not exercised over computer systems, nor are all laboratory data retained. For example, data from the FTIR, TOC, and particle size analyzer instruments could be deleted or altered. Further, the firm told the FDA that they discovered that the database, usage logs, and audit trails had been deleted from the high accuracy particle counter instrument. Lab records did not include signatures to confirm that electronic chromatographic data were reviewed to ensure completeness, accuracy, and compliance. At issue is more than 700 additional injection sequences without signature. FDA states that “The extent of the data integrity violations throughout your facility remains unknown.” NB: Remember that much of this came to light during the legal tussles between Fresenius and Akorn in the past couple of years.
  • Operators displayed poor aseptic practices during set up and filing operations for sterile products. Numerous examples of poor practices when making connections are provided. Further interventions are not appropriately simulated during media fills. FDA references the FDA Guidance on Aseptic Processing and provides a link to this in the warning letter.
  • Batch records did not include complete information. For example, a leak during filling was not noted, nor were significant filling machine interventions noted.
  • FDA also notes that “Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture.” FDA asks them to provide responses to what has become FDA’s standard long version boilerplate regarding remediation of data integrity failures.
  • The firm must review all internal audits conducted at Akorn facilities for the past five years and certify that the required corrective actions have been taken. If the corrective actions have not been completed, they are to provide a timeline for these activities. The certification should be signed by the CEO of Akorn.
  • Based on the repeated failures at multiple sites, the FDA determined that “management oversight and control over the manufacture of drugs are inadequate.”

DRUGS | US Pharmaceuticals, Inc

US Pharmaceuticals, Inc (Belleville, NJ) received a warning letter on June 6, 2019, based on the outcome of an inspection ending December 18, 2018. The firm manufactures OTC products.

FDA states that the Quality systems are inadequate, and recommends they retain qualified consultants to assist them in coming into GMP compliance.

Deficiencies include but are not limited to:

  • An investigation into failing microbial and chemical monitoring of the firm’s purified water system was not adequate. Ten instances of failing chemical results were not investigated.  The microbial problems with the system traced back to 2016 and were never adequately remediated and yet water produced by the system continued to be used to manufacture OTC products.
  • The purified water system is not adequately designed and operated to produce water that met specifications. FDA cited similar shortcomings during a 2010 inspection.
  • Sampling of the water system was not adequate, or representative of its actual use. For example, since August 20017, it was sampled post sanitization, and it was not sampled using a hose which was used during routine manufacture.

DRUGS | AllerQuest LLC

AllerQuest LLC (Plainville, CT) received a warning letter on June 24, 2019, based on the outcome of an inspection ending March 1, 2019. This is an unusually quick enforcement action driven by the potential impact of the severity of the inspection observations.

  • The facility is not adequate for the production of sterile drugs. Doors between the ISO 5 critical area and an uncontrolled space have gaps in multiple locations. The aseptic line has limited protection and “…a high degree of exposure to contamination hazards from manual intervention and the surrounding air.” The warning letter identifies a long list of problems and activities that the firm must perform.
  • The firm had a variety of environmental action limit excursions within the ISO 5 area and did not adequately address them. These included cleaning and disinfection, EM and personnel monitoring, temperature, humidity, and pressure excursions.
  • The firm identified repeated contamination of injectable drug product with foreign particulates, including glass or aluminum, from the manufacturing process. These were not adequately investigated or remediated.
    • Further, FDA states, “There is a lack of assurance of the quality of your drug products. For example, during one of your quality assurance audits following 100% visual inspection, additional particulate contamination was found that was not identified during a previous 100% visual inspection conducted for lot release. In addition, you repeatedly discarded contaminated ampules identified from visual inspection, sometimes exceeding 10% of a batch, and then distributed the remainder of the batch. The high percentage of rejected ampules and particulates found in cleared ampules after 100% visual inspection indicate that you may have released drug product that contains particulates.”

DEVICES | Clinicon Corp

Clinicon Corp (Oceanside, CA) received a warning letter on June 20, 2019, based on the outcome of an inspection ending April 4, 2019. The firm manufactures Class II, sterile, single-use laser accessory probes.

Deficiencies include but are not limited to:

  • The firm did not provide validation documentation for packaging of the sterile device. At issue is the maintenance of the device sterility.
  • The firm does not calibrate or maintain the heat sealer used to create a sterile barrier for the laser probe device.
  • The firm could not provide evaluation or approvals for suppliers of raw materials for the device distributed since 2012. 
  • The firm could not provide a procedure describing how DHRs are maintained, nor could they provide records demonstrating these activities had been performed for the distributed probes.

BIMO | Abington Memorial Hospital, IRC

Abington Memorial Hospital, IRC (Abington, PA) received a warning letter issued by CBER on June 24, 2019, based on the outcome of an inspection of the IRB ending February 15, 2019.

Deficiencies include but are not limited to:

  • When expedited reviews are conducted, they do not include at least one member of the IRB whose primary concerns are non-scientific.
  • The IRB failed to prepare and maintain adequate documentation of their activities; specifically, the meeting minutes (and there is a whole laundry list of them) do not adequately document the presence or absence of members listed in the voting roster.  
  • FDA states that the shortcomings identified in the current inspection are the same or similar to those from previous inspections and thus the IRBs corrective actions, if any, were not effective.


Imprimis NJOF, LLC received a warning letter on June 7, 2019, based on the outcome of an inspection ending July 10, 2017. This is not the first enforcement action against the firm. The warning letter identifies failures to meet the conditions of section 503B as well as failure to meet the requirements of 21CFR 211. Also, FDA cites the firm for sale of unapproved new drugs, misbranded drugs, failure to report drugs compounded by the site, and failure to report adverse events consistent with 21CFR 310.305. The firm has received four previous warning letters starting in 2017: