After receiving several Form 483 letters from the Food and Drug Administration to bring a list of items into voluntary compliance, the FDA sent Zimmer Biomet a warning letter late last month regarding corrections that need to be made at the company’s North Warsaw campus.

The letter, sent to Zimmer Biomet President and CEO Bryan Hanson and dated Aug. 24, listed five observations of unacceptable procedures in the manufacturing and packaging process. Much of the information in the letter is redacted to protect the company’s proprietary interests.

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Among the processes observed on April 9 were:

• An employee was observed using a nylon brush to clean devices, when a wire brush is required.

• An employee was packing finished devices and used an incorrect gauge to measure the tray seal in the metal packaging area. The employee said the gauge was the only one provided at that work station.

• “A sterile sealing process was observed. An employee was performing sealing operations using a (name redacted) sealer. The employee was not able to demonstrate how to measure seal width using a gauge as required your Package Requirements - I00051.3. The operator incorrectly measured an area outside of the blister package seal.”

On April 11, the FDA said in its letter, “We observed the sterile packaging operation using sealer (redacted item). This sealer was identified as a legacy sealer whose process validation was found to be inadequate. Your firm has been relying on appropriate process monitoring to justify the continued use of this sealer.”

On April 17, the FDA inspectors said, “An employee was observed measuring part (redacted), for specification (redacted) as part of their line clearance activities. According to drawing, (redacted), specification (redacted) upper limit should measure (redacted) with a tolerance (redacted). The employee measured this specification (redacted) for the first part as (redacted) and the second part as (redacted) and stated the part was ‘good.’

“These measurements were not identified as non-conformances until the operator was directly asked what the specification was and if the parts were conforming.”

The letter also cited a “failure to establish and maintain design validation procedures to ensure proper risk analysis is completed, as required by 21 CFR 820.30(g).

“For example, during the inspection, we reviewed a Process Failure Mode Effects and Criticality Analysis (PFMECA) #PF0700, dated November 2, 2017, as part of the design history file for your comprehensive shoulder implant, (product: XL-115363). This review confirmed inconsistencies in the assignment of potential severity ratings for hazards identified during design review.”

After citing another example, the letter said the FDA is concerned that recent design reviews conducted by Zimmer Biomet continues to demonstrate inconsistencies.

The fifth item in the letter expressed the FDA inspector’s concern where environmental conditions could reasonably be expected to have an adverse effect on product quality, the company has failed to establish and maintain procedures to adequately control the environmental conditions as required.

But the report went on to say, “Your response indicates that you have updated your procedures to ensure investigations into excursions are investigated and documented properly. You also indicated that your firm has discontinued the use of mailboxes and opened CAPA CA-04521 to address employee practices in this area.

”We will need to verify during a re-inspection that these actions are effective in ensuring environmental conditions are being controlled properly.”

The letter went on to say the company should take prompt action to correct the violations without further notice, and notify the FDA within 15 days of the date of the letter what steps have been taken; if the steps are to be taken over time, a timeline would need to be included.

The final paragraph of the letter said the warning “is not intended to be an all-inclusive list of the violations at your firm’s facility.”



Company Response

In response, Zimmer Biomet Vice President of Corporate Communications Monica Kendrick said the company filed an 8-K form with the Securities and Exchange Commission. It said:

“On August 24, 2018, a subsidiary of Zimmer Biomet Holdings, Inc. received a Warning Letter from the U.S. Food and Drug Administration related to observed non-conformities with current good manufacturing practice requirements of the Quality System regulation at our North Campus manufacturing facility in Warsaw (Warsaw North Campus).

“We take the matters identified in the Warning Letter seriously and are in the process of preparing a written response to the Warning Letter.

“The Warning Letter is specific to our Warsaw North Campus facility. As previously disclosed, the FDA performed an inspection of the Warsaw North Campus facility in 2016 and issued a Form 483 with inspectional observations at the conclusion of the inspection in late 2016. Also as previously disclosed, the FDA performed a re-inspection of the Warsaw North Campus facility in April 2018 and issued a Form 483 with inspectional observations at the conclusion of the re-inspection. We have provided written responses to the FDA detailing corrective actions underway to address the FDA’s observations and have provided, and will continue to provide, regular updates to the FDA regarding our quality remediation plan at the Warsaw North Campus. While the Warning Letter acknowledges our quality remediation plan and actions we’ve already taken to address the FDA’s inspectional observations, it notes violations that require additional action or explanation. In the Warning Letter, the FDA proposes a Regulatory Meeting with us to discuss the proposed corrections.

“We will continue to work expeditiously to address the issues identified by the FDA and we intend to respond within fifteen business days to the Warning Letter. We expect that the proposed Regulatory Meeting will take place subsequent to the submission of our written response to the Warning Letter. Meanwhile, the Warning Letter does not restrict production or shipment of products from the Warsaw North Campus facility or require the withdrawal of any product from the marketplace. Nor does it restrict our ability to seek FDA 510(k) clearance of products. The Warning Letter states that requests for Certificates to Foreign Governments will not be granted until the violations have been corrected. Additionally, premarket approval applications for Class III devices to which the Quality System regulation violations are reasonably related will not be approved until the violations have been corrected. We presently have no such applications before the FDA.

“We believe that the FDA’s concerns set forth in the Warning Letter can be resolved without a material impact to our financial results. We cannot, however, give any assurances that the FDA will be satisfied with our response to the Warning Letter or as to the expected date of the resolution of the matters included in the Warning Letter. Until the issues cited in the Warning Letter are resolved to the FDA’s satisfaction, the FDA may initiate additional regulatory action without further notice. Any adverse regulatory action, depending on its magnitude, may restrict us from effectively manufacturing, marketing and selling our products and could have a material adverse effect on our business, financial condition and results of operations.“

Kendrick said, “We do not have anything to add at this time.”

Officials at the FDA were asked via email what the next step would be if inspectors weren’t satisfied, but a response hadn’t arrived by press time.

Link to the FDA warning letter: https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm618429.htm

Link to Zimmer Biomet response to the SEC: http://otp.investis.com/clients/us/zimmer_biomet/SEC/sec-show.aspx?Type=html&FilingId=12935284&CIK=0001136869&Index=10000.