The US Food and Drug Administration (FDA) on Tuesday released the warning letter it sent to Israel-based Teva Pharmaceuticals earlier this month, noting instances of data deletion and manipulation at the company’s manufacturing site in Gödöllő, Hungary.
Last week, Teva disclosed in an SEC filing that it had received a warning letter on 14 October (four months after the site was banned from shipping products to the US), but now the details of that letter have revealed not only data integrity questions (including “quality-related documents in a waste bin”) but inconsistencies in assessing sterility failures and poor aseptic processing techniques.
Teva spokeswoman Denise Bradley told Focus: “In January, we made a decision to voluntarily stop all production at the plant while we evaluated and responded to FDA’s observations. Since that time, Teva has been using a systems-based approach with respect to our remediation efforts, focused on manufacturing and lab processes. Our corrective actions address both the specific concerns raised by investigators as well as the underlying causes of those concerns. Our communication with the FDA is ongoing.
“We are also actively working to replenish critical and priority products as quickly as possible, in some cases by transferring products to other Teva manufacturing sites and, -- as needed – by identifying alternate suppliers for products in short supply or out of stock,” she added.
Warning Letter Details
The seven violations outlined in the letter include Teva’s failure to identify microorganisms found in the contaminated units, “an operator sitting on the clean room floor during set-up of the filling line and not changing the gown after standing up,” and “operators leaning against the cleanroom walls.”
In addition, FDA investigators found colony counts for environmental and personnel monitoring that did not match Teva’s official records.
“Inaccurate reporting of environmental and personnel monitoring data undermines your ability to evaluate and maintain a state of control in your aseptic processing operation,” FDA says.
The agency also noted that the site’s stand-alone computer systems lacked controls, such as routine audit trail review and full data retention, to prevent analysts from deleting data.
“Although you implemented a procedure to begin reviewing audit trails of your high performance liquid chromatography (HPLC) Empower system on January 11, 2016, you had not performed any reviews prior to our inspection,” the warning letter reads.
FDA Warning Letter for Czech Drugmaker
FDA on Tuesday also released a warning letter dated 18 October for Czech Republic-based Interpharm Praha, outlining the site’s serious data manipulation violations.
“Your quality control unit did not have basic controls to prevent changes to your electronically-stored laboratory data. Your analysts had user privileges to the Empower-2 system used to generate and analyze chromatographic data that allowed them to eliminate failing, atypical and satisfactory results with no notification; alter peak areas; and add or eliminate samples from sequences without authorization,” the warning letter reads.