Just a quick update – the FDAzilla Enforcement Analytics database was updated with data through April 25, 2017. We typically refresh the inspections data every 3 weeks or so, pair new warning letters with inspections every week, and add new 483s, EIRs, and 483 response letters every month.
We took a snapshot of the 7 warning letters the FDA sent to pharmaceutical companies last month. Drug manufacturing violations ranged from “products being misbranded” to sites “not ensuring that test procedures are scientifically sound.”
From pharmaceuticals in India, Pennsylvania, and more, here they are (starting with the most recent): Continue reading →
The FDA has been writing up companies on data integrity since the year 2000. Even after all the horror stories, and even after billions of dollars of market cap have been erased from it, here we are in 2017, still talking about it.
Here is some troubling text from recent Warning Letters that cite data integrity:
“…our investigator observed your warehouse supervisor tearing out pages from your firm’s annual report and placing the pages into his pocket.”
The MHRA publisheda large slide deck that addressed GMP deficiencies identified during inspections in 2016. They published a slide deck of similar information for 2015 a few months ago. In this blog, we look at some of the similarities and differences between the two years. The data only represent deficiencies noted for dosage forms and do not include those identified at inspections of API manufacturers. We previously compared the FDA inspection observations for 2016 with the 2015 MHRA Deficiencies.
In 2015 we published a collection of FDA GMP warning letters that included deficiencies in data governance and data integrity. Here we provide the same information for 2016 drug GMP warning letters. These should serve as a resource for GMP audit staff and QA staff as they evaluate their own firms and contract sites for gaps in these areas. In this introduction, we provide tables and graphs identifying the dates of the warning letters, firms to which they were issued, and the country where the facility is located. We also provide a table that shows the trends over time for location of countries where facilities receiving these warning letters were located, beginning in 2008. And, finally, we provide a tabulation of the regulations most frequently cited for these deficiencies in 2015 and 2016.
We took a snapshot of the 8 warning letters the FDA sent to pharmaceutical companies last month. Drug manufacturing violations ranged from failing to monitor the water purification system to personnel not wearing appropriate clothing to prevent contamination.
From pharmaceuticals in California, Singapore, and more, here they are: Continue reading →
New data synthesized by FDAzilla has revealed several dramatic shifts with FDA inspection and enforcement activity.
The FDA issued 15 pharma GMP-related warning letters to manufacturing sites in China in 2016 – a 5-fold increase from years prior. China averaged 2.7 Warning Letters per year from 2013 to 2015. This explosion was led mostly by infamous FDA investigator, Peter Baker, who performed 17 inspections in China in 2016, leading to 13 FDA Form 483s and 4 Warning Letters. Continue reading →
In October 2014, the FDA published a final Guidance for Industry, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection. Publishing this guidance was a requirement of section 707 of the Food and Drug Administration Safety and Innovation Act (FDASIA). Section 707 of FDASIA adds 501(j) to the Food, Drug, and Cosmetic Act (FD&C Act) to deem a drug adulterated if it “has been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.” Before that time and since, the FDA cited instances where firms have delayed inspections or denied investigators access to areas or documents that they should be able to view.
In this section, we will address policies and guidance that the FDA has published since the end of 2013, look at enforcement activities in this area, and make some predictions for the future of this market segment.
Part of a comprehensive GMP Intelligence program is the monitoring of enforcement actions, including FDA 483s, warning letters, recalls, import alerts, consent decree agreements, and EU reports of GMDP noncompliance. This article presents the most recent GMP inspection data from CDER and MHRA. The CDER data are from inspections conducted in FY2016 and the MHRA data come from inspections conducted in 2015.
The New England Compounding Center (NECC) preparation and shipment of contaminated injectable products across state lines in 2012 created a firestorm of publicity and enforcement actions. More than 750 patients in twenty states developed a fungal infection, fungal meningitis, and more than 60 people died. Others became sick and suffered long term harm as reported by Kurt Eichenwald in a Newsweek article of April 2015. In an abundance of caution, FDA quickly recommended that healthcare providers not use any product from NECC. The FDA commissioner gave testimony before Congress in November 2012 where they outlined their response and presented FDA’s legal authority over compounded drugs. In December 2014 fourteen arrests were made. The owner of the pharmacy was indicted by a federal grand jury and is currently on trial. He faces racketeering charges and twenty-five counts of second decree murder. In May 2015, a federal bankruptcy judge approved a $200 million fund to provide compensation to victims. A recent article from the Wicked Local Framingham written by Walter F. Roche Jr., identifies some of the practices that have come to light at the trial. This event triggered legislative changes, development of more than two dozen guidance documents, and changes in inspection practices for a niche area of drug preparation within the United States.
Preparing for GMP inspections, particularly pre-approval inspections, can be a challenge when resources are limited and staff may have little expertise in these important activities. This becomes especially complex for start-up companies that are virtual, or essentially virtual, and rely on contract manufacturers and contract laboratories. Virtual firms are responsible for the content of the submission, release of product to the clinic or for commercial distribution and post approval safety reporting even though they may not manufacture API or dosage form. The following are some suggestions for these firms to ensure a successful inspection outcome when they have limited experience in this activity and limited resources:
Forms 483 Addressing Sterility Assurance and Cross-Contamination
Along with data integrity, deficiencies in sterility assurance and the potential for product or API contamination identified during FDA inspections often lead to warning letters. Also many product recalls are based on lack of sterility assurance or less frequently on potential cross contamination. Here we take a look at six forms 483 that include observations associated with sterility assurance and potential cross contamination. These are certainly not meant to provide an all-inclusive view of the topic, but rather represent recent inspection observations in these areas to demonstrate the broad scope of the topic. FDA’s flurry of inspections and enforcement actions against compounding pharmacies and outsourcing facilities focuses heavily of requirements associated with expectations regarding aseptic manufacture of sterile drug products. These sites are often also cited for the potential for cross contamination. Lack of sterility assurance and the potential for cross contamination, particularly by high potency compounds or sensitizing agents both have potentially serious consequences for patient safety. Many compounding pharmacies and outsourcing facilities have recalled large numbers of products due to concerns about sterility assurance. We include one example of this type of facility in the collection presented below. Failure to complete adequate cleaning validation for multi-product equipment is often another source of potential cross contamination even when products do not include high potency compounds or sensitizing agents.