WARNING LETTER
Phillips Precision, Inc.
MARCS-CMS 697119 —
December 09, 2024
Delivery Method:
VIA Electronic Mail
Product:
Medical Devices
Recipient:
Recipient Name
Jeanne M. Phillips
Recipient Title
Owner and CEO
Phillips Precision, Inc.
7 Paul Kohner Pl
Elmwood Park
,
NJ
07407
United States
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
CMS # 697119
December 9, 2024
Dear Ms. Jeanne M. Phillips:
During an inspection of your firm located in Elmwood Park, NJ on April 22, 2024 through July 17, 2024, investigators from the United States Food and Drug Administration (FDA) determined that your firm contract manufactures orthopedic implants and instruments. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,
Code of Federal Regulations
(CFR), Part 820.
We received a response from Ms. Shalyn Creighton, Quality Assurance and Regulatory Compliance Manager, dated August 8, 2024 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a).
Specifically, you either failed to adequately implement or define and document requirements for your “Master Validation Plan Process and Software Validation” procedure (SOP-34; Rev. M and O; Effective: 6/13/14 and 5/9/19) which governed process validations for the
(b)(4)
Cleaning Machine “
(b)(4)
” (model #
(b)(4)
, serial #
(b)(4)
) and
(b)(4)
processes. For example:
A. Cleaning validations conducted for the “
(b)(4)
” used to
(b)(4)
clean orthopedic implants and instruments, for which your firm functions as the final cleaner for
(b)(4)
out of
(b)(4)
top customers, do not provide adequate assurance that the process consistently produces product that meets specifications. For example:
1. You failed to adequately implement sections 5.3.7 and 5.3.9.3 of your process validation procedure (SOP-34; Rev. M) which required you to challenge your cleaning process under the worst-case product and process conditions during the operational qualification (OQ) of your “
(b)(4)
” conducted under “Final
(b)(4)
Cleaning Operational Qualification (OQ) Protocol” (OQ_920-001; Rev. B; Approved 2/5/15), which includes the report. For example:
i. Although your performance qualification (PQ) protocol required cytotoxicity, endotoxin, and particulate testing for the “
(b)(4)
” to demonstrate that cleanliness requirements were consistently met, you failed to conduct such testing during OQ which is defined in your procedure as “***documented verification that equipment performs in accordance with manufacturer’s specifications and process operating at [sic] the extremes of the equipment or process operating capabilities***.”
ii. You failed to adequately challenge the cleaning process under worst-case process parameters and product based on types and/or geometries, surface finishes, and processes conducted during OQ. For example, you did not challenge
(b)(4)
as all loads were run at
(b)(4)
; system
(b)(4)
quality above
(b)(4)
microsiemens/ cm; clean time below
(b)(4)
minutes; and load weight above
(b)(4)
pounds. You also failed to define the worst-case setting for degassing time in the OQ protocol which your firm’s management stated is under
(b)(4)
minutes as well as document the degassing time during OQ.
In addition, you executed work orders during OQ without the
(b)(4)
manufacturing process, which your firm’s management identified during the inspection as a process that challenges your firm’s surface finishes and equipment process capabilities in
(b)(4)
out of
(b)(4)
work (WO #: 99343, 99284, 99336, and 98026-1) which were provided as worst case products.
Furthermore, our investigator observed adhesive tape on the proximal femur left plasma implant (PF-2000L-02M; WO 102275) in the finishing department on 4/26/24. However, your OQ did not include challenges associated with the removal of adhesives and your “Final
(b)(4)
Cleaning (
(b)(4)
)” (WI-920-001; Rev. K; Effective: 12/10/21) does not establish cleaning specifications associated with this process.
iii. You failed to define or document the load configuration for work orders 65926 (
(b)(4)
devices), 64205 (
(b)(4)
devices), 63988 (
(b)(4)
devices), 65917 (
(b)(4)
devices), 65921 (
(b)(4)
75 devices), and 65791 (
(b)(4)
devices) in the OQ protocol and report in that your firm could not determine if devices were put in a single cleaning load or broken up into multiple
(b)(4)
. In addition, you failed to challenge different loading configurations that your firm’s management stated are used during routine production such as the use of
(b)(4)
which is allowed in section 5.2.4.2.6 of your “Final
(b)(4)
Cleaning (
(b)(4)
)” (WI-920-001; Rev. K; Effective: 12/10/21) and
(b)(4)
. On 4/26/24, our investigator observed the tibia stylus assembly instrument (Part #
(b)(4)
; WO 101881) enclosed in a
(b)(4)
and the
(b)(4)
instrument (Part #
(b)(4)
; WO 98151) placed on top of a
(b)(4)
, neither of which were evaluated during OQ.
2. You failed to adequately implement section 5.3.9.4 of process validation procedure (SOP-34; Rev. M) which required “***documented evidence that a process system performs as intended and that it demonstrates the capability to consistently meet appropriate specifications***” for the performance qualification (PQ) of your “
(b)(4)
” conducted under “Final
(b)(4)
Cleaning Process Qualification (PQ) Protocol” (PQ_920-001; Rev. B; Approved 3/30/15), which includes the report. For example:
i. As specified in section 5.2.2 of your “Final
(b)(4)
Cleaning (
(b)(4)
)” procedure (WI-920-001; Rev. K; Effective: 12/10/21), you are to ensure that the system
(b)(4)
quality of the rinse tank is below (≤
(b)(4)
microsiemens/cm) during normal operation of your
(b)(4)
cleaner. However, you failed to conduct PQ under normal operating conditions for system
(b)(4)
quality in that only
(b)(4)
out of
(b)(4)
runs were run at ≤
(b)(4)
microsiemens/cm while the remaining cycles were run at
(b)(4)
and
(b)(4)
microsiemens/cm. In addition, you failed to define the optimal setting for degassing time in the PQ protocol as well as document the degassing time during execution of your PQ.
ii. You failed to utilize
(b)(4)
and
(b)(4)
which were sufficiently representative of manufactured devices. For example, WO # 99284 (Part #
(b)(4)
) includes surface finishes such as vibratory, deburring, and finishing and equipment processes such as
(b)(4)
, assembly, machine, and
(b)(4)
; however, these processes were not represented in the
(b)(4)
and
(b)(4)
utilized during your PQ and your firm did not document justification for the equivalency of those
(b)(4)
and
(b)(4)
through objective evidence.
3. You failed to adequately implement section 5.1 of your process validation procedure (SOP-34; Rev. M) which requires a completed process failure modes and effects analysis (PFMEA) as a part of an approved validation plan and for which the definition under section 5.3.14 indicates that a PFMEA is used to “***assess quality risk levels to each step in a manufacturing process***” with a reference to your “Risk Management” procedure (SOP-35; Rev. K; Effective: 3/9/15) which outlines the criteria for severity scores on a scale of
(b)(4)
through
(b)(4)
. For example, per section 10.4 of the “Final
(b)(4)
Cleaning Validation Plan” (VP_920_001; Rev. D; Effective: 3/31/15) for the “
(b)(4)
”, you utilized a PFMEA to assess quality risk levels that “***reflect[ed] the worst case process (for both clean and rinse) via processing***at maximum loading conditions (i.e. weight) for variable
(b)(4)
states @
(b)(4)
,
(b)(4)
, and
(b)(4)
***.” However, you assigned a severity of
(b)(4)
(
(b)(4)
) out of
(b)(4)
for all but one of the failure modes for devices cleaned with your “Zenith” without determining if your firm was the final clean and if a severity score of 4 was appropriate. Your firm did not learn that it was the final clean for
(b)(4)
out of
(b)(4)
of your top customers until this information was requested during the inspection on 5/2/24. As of the close of the inspection, your firm had not evaluated the 8 other customers you have manufactured for since 2020 to determine if your firm is the final clean for them as well. For the 4 top customers for which your firm was the final cleaner, your firm manufactured and shipped
(b)(4)
implants and
(b)(4)
instruments for Customer
(b)(4)
;
(b)(4)
implants and
(b)(4)
instruments for Customer
(b)(4)
;
(b)(4)
implants and
(b)(4)
instruments for Customer
(b)(4)
; and
(b)(4)
instruments for Customer
(b)(4)
.
B. You failed to adequately implement 5.3.8 of your process validation procedure (SOP-34; Rev. O) which requires “***documented evidence providing high degree of assurance that a process***will consistently perform as intended” in that:
1. You have not conducted a process validation for additional post-production final cleaning processes listed in the “Final
(b)(4)
Cleaning (
(b)(4)
)” procedure (WI-920-001; Rev. K; Effective: 12/10/21), which allows for the use of
(b)(4)
and
(b)(4)
, to provide adequate assurance that the process will consistently produce product that meet specifications. For example, on 4/22/24 and 4/26/24, our investigator observed your operators using
(b)(4)
and
(b)(4)
to wipe devices which had already been cleaned on the “
(b)(4)
”.
2. The “Validation Plan for
(b)(4)
” (VP_920-012; Rev. C; Effective: 6/18/19) only included devices composed of
(b)(4)
and
(b)(4)
stainless steel and did not include devices composed of titanium (which your firm’s management stated are also treated with
(b)(4)
during manufacturing) or documented justification for why validation of such devices was not necessary.
C. You failed to adequately implement section 5.3.9.4 of your process validation procedure (SOP-34; Rev. M and O) which required “***documented evidence that a process system***demonstrates the capability to consistently meet appropriate specification***” and “***how/when samples will be taken, labeled, transported, and tested***” for the performance qualification (PQ) of your “
(b)(4)
”. For example:
1. Your “Final
(b)(4)
Cleaning Process Qualification (PQ) Protocol” (PQ_920-001; Rev. B; Approved 3/30/15), which includes the report, for the “
(b)(4)
” did not utilize a sampling plan based on a valid statistical rationale for cytotoxicity, endotoxin, and particulate testing. Although your “PPI Sampling Plan” procedure (DOC-03; Rev. E; Effective: 12/10/14) requires you to use an AQL of
(b)(4)
unless otherwise specified, the number of
(b)(4)
tested per lot for cytotoxicity and endotoxin was
(b)(4)
and
(b)(4)
, respectively and the number of
(b)(4)
units tested for cytotoxicity, endotoxin, and particulate was
(b)(4)
, and
(b)(4)
, respectively. An AQL of
(b)(4)
for a sample size of
(b)(4)
and
(b)(4)
units per lot would have required testing on
(b)(4)
samples per lot for each test.
2. Your “Validation Plan for
(b)(4)
” (VP_920-012; Rev. C; Effective: 6/18/19) did not utilize a sampling plan based on a valid statistical rationale. Although your “PPI Sampling Plan” procedure (DOC-03; Rev. E; Effective: 12/10/14) requires you to use an AQL of
(b)(4)
unless otherwise specified, cytotoxicity testing was only conducted on
(b)(4)
out of
(b)(4)
per lot and endotoxicity and particulate testing was conducted on
(b)(4)
per lot. An AQL of
(b)(4)
would have required a sufficient number of samples to be able to test a minimum of
(b)(4)
samples each for endotoxins, cytotoxicity, and particulates for a lot size between
(b)(4)
and
(b)(4)
.
We reviewed your firm’s response and conclude that it is not adequate.
With regards to the OQ for the “
(b)(4)
”, you plan to update the
(b)(4)
cleaning procedure and perform a revalidation which will challenge: the minimum and maximum critical process parameters with worst-case product and process
(b)(4)
; removal of any adhesives; load configurations; comingling; multiple
(b)(4)
; and
(b)(4)
. However, there was no confirmatory statement that you plan to conduct cytotoxicity, endotoxin, and particulate testing during OQ or rationale for why this would not be necessary and explanation provided for use of worst-case product and process
(b)(4)
instead of actual products during OQ.
With regards to PQ for the “
(b)(4)
”, you dispute that
(b)(4)
purity of the rinse tank was not conducted at nominal; however, the
(b)(4)
and
(b)(4)
cycle was not done under normal operating conditions. You plan to update the
(b)(4)
cleaning procedure and perform a revalidation to include notation of the degassing time and use of worst-case product
(b)(4)
. However, there was no corrective action identified to run system
(b)(4)
purity under normal operating conditions (≤
(b)(4)
microsiemens/cm) and define the optimal degassing time.
With regards to the PFMEA for the “
(b)(4)
”, you intend to review and update the existing PFMEA as needed; contact
(b)(4)
of the
(b)(4)
customers you still do business with to determine whether your firm is the final clean and request their risk assessment; and do the same for any new customers in the future. However, there was no corrective action identified to proceduralized these actions. Furthermore, it is not clear whether you plan to update the respective severity scores for the process failure modes of the “
(b)(4)
”, for customer devices for which you are determined to be the final clean, in order to establish adequate quality risk levels.
With regards to
(b)(4)
, you plan to “amend” the
(b)(4)
validation to include devices composed of titanium. However, it is unclear what the difference is between an amendment and a revalidation.
With regards to process validation for additional post-production cleaning processes, you state that the use of
(b)(4)
, and (medical grade)
(b)(4)
to wipe post-production and post-final-cleaning is done in accordance with customer requirements. However, no supporting evidence was provided and rationale for why post-production final cleaning processes would be needed if the final cleaning process is meant to assure that cleaning requirements can consistently be met.
With regards to sampling, you plan to update the process validation procedure and ensure that the revalidation of the “
(b)(4)
” and amendment of the
(b)(4)
validation will utilize a statistically valid sampling plan based on documented rationale.
You have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
2. Failure to establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications when deviations from device specifications could occur as a result of the manufacturing process, as required by 21 CFR 820.70(a).
Specifically, you failed to implement your “Final
(b)(4)
Cleaning (
(b)(4)
)” (WI-920-001; Rev. K; Effective: 12/10/21). For example:
A. You failed to implement section 5.2.4.2.5 which states “
(b)(4)
.” For example, on 4/26/24, our investigator observed comingling of the large
(b)(4)
instrument (Part #
(b)(4)
; WO 101395) and
(b)(4)
instrument (Part #
(b)(4)
; WO 99014) in the same
(b)(4)
load.
B. You failed to implement section 5.2.4.2.1 which states “Do not stack product.” For example, on 4/26/24, our investigator observed two instances where devices were stacked upon each other within a cleaning load:
(b)(4)
release instrument (Part #
(b)(4)
; WO 98145) and
(b)(4)
instrument (Part #
(b)(4)
; WO 98151), which appeared be stacked in 3 layers. In addition, the “
(b)(4)
" manual specifically states that “
(b)(4)
.”
We reviewed your firm’s response and conclude that it is not adequate. You plan to perform a revalidation on the “
(b)(4)
” to include challenges such as comingling and load configurations during OQ and review and update the PFMEA and
(b)(4)
cleaning procedure, as applicable. However, you have not provided any timelines for completion of any of your corrective actions and there was no corrective action identified to address that your employees were not following procedures. Furthermore, it is not clear how a revalidation on the “
(b)(4)
” that challenges comingling will address the original purpose which was to
(b)(4)
, as noted in your
(b)(4)
cleaning procedure. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
3. Failure to adequately establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b).
Specifically:
A. You have not defined and documented procedures to monitor and control the following parameters for the validated
(b)(4)
Cleaning Machine “
(b)(4)
” (model #
(b)(4)
, serial #
(b)(4)
) used to clean orthopedic implants and surgical instruments, for which your firm functions as the final cleaner for
(b)(4)
out of
(b)(4)
top customers:
1.
Weight of the Load
(b)(4)
:
There is no procedure to ensure that the load
(b)(4)
weight is below
(b)(4)
pounds, which was determined to be the limit during validation.
2.
Batch-to-Batch Temperature of the Cleaning Solution (i.e., Detergent) in the Clean and Rinse Tanks:
There is no procedure to ensure that temperatures of the cleaning solution in the clean and rinse tanks between runs do not exceed the temperature limit of
(b)(4)
℉, which was determined to be the limit during validation.
3.
Concentration of the Cleaning Solution (i.e., Detergent):
There is no procedure to ensure that the concentration of cleaning solution is monitored and controlled on a
(b)(4)
basis (with the use of a titration kit or other suitable means) to ensure adequate cleaning, which was specified during validation to be established per manufacturer’s instructions.
4.
Time for Degassing of Cleaning Solution (i.e., Detergent):
There is no procedure to ensure that your “
(b)(4)
”, which operates at
(b)(4)
kHz, is degassed for
(b)(4)
to
(b)(4)
minutes before use for effective cavitation, which was specified during validation to be established per manufacturer’s instructions.
B. You failed to implement sections 5.2.1.2 and 5.2.2.4 of your “Final
(b)(4)
Cleaning (
(b)(4)
)” procedure (WI-920-001; Rev. K; Effective: 12/10/21) which requires verification of the temperature of the cleaning solution (i.e., detergent) in the clean and rinse tanks to ensure it is in the validated range of
(b)(4)
℉ to
(b)(4)
℉ and documentation of the temperature on the “
(b)(4)
Cleaning System Daily Temperature Log” (Form-03_01; Rev. F; Effective: 5/25/19) during startup of your “
(b)(4)
”. Overall, review of the temperature log from January 2, 2023 and March 26, 2024 revealed that approximately
(b)(4)
% (
(b)(4)
out of
(b)(4)
) of the loads run on your “
(b)(4)
” were performed at out of specification temperatures. For example, your employees operated your
(b)(4)
cleaner at temperatures lower than the minimum specified limit of
(b)(4)
℉ on 2/28/23; 4/6/23; 4/25/23; 5/19/23; 5/20/23; 5/22/23; 5/24/23; and 7/1/23, implicating at least
(b)(4)
orthopedic devices (
(b)(4)
implants and
(b)(4)
surgical instruments).
C. You have not established a procedure for the monitoring and control of temperature and time for
(b)(4)
. Section 6.2 of your “
(b)(4)
” procedure (WI-920-005; Rev. F; Effective: 9/6/17) states that the “***
(b)(4)
is pre-heated***between
(b)(4)
and
(b)(4)
F for a minimum of
(b)(4)
prior to application.”
We reviewed your firm’s response and conclude that it is not adequate.
With regards to the inadequate monitoring and control of the above parameters, you plan to reevaluate monitoring and controls after revalidation of the “
(b)(4)
”; update the frequency as needed; and revise the
(b)(4)
cleaning procedure to establish the applicable batch-to-batch temperature for the tanks.
With regards to out of specification temperature recordings, you explain the temperatures would have increased as the morning went on such that only the first one or two runs of each day would have been affected; your employee may have misunderstood the process and either was not fully aware of the minimum temperature and/or what to do in the event the temperature was below the limit; and that because the minimum temperature proposed in the user manual is
(b)(4)
℉ and that the
(b)(4)
cleaning action only begins to deteriorate when temperatures go above certain limits (typically
(b)(4)
℉), the risk of impact to the parts cleaned on the specified days is low. However, there were temperatures noted above the validated temperature range of
(b)(4)
℉ on 8/18/23; 10/10/23; 1/15/24; 2/1/24; and 4/1/24. Additional temperatures below
(b)(4)
℉ were also noted on 8/7/23; 8/12/23; 8/24/23; and 11/3/23.
You also plan to update the
(b)(4)
cleaning procedure to include an explanation of what to do in the event the temperature is below the minimum temperature; train applicable employees as well as to the nonconforming product procedure to identify nonconformances regarding parts themselves; and update the PFMEA to include the risks associated with parts processed outside of the specified temperature limits. However, there were no corrective actions identified to (1) address that your employees were not following procedures to ensure that the startup temperatures were within specified limits and (2) update the
(b)(4)
cleaning procedure to specify how long employees should wait before measuring the temperature for verification before use of the
(b)(4)
cleaner.
With regards to the inadequate monitoring and control of parameters for
(b)(4)
, you plan to review the
(b)(4)
validation and establish the applicable monitoring and control and amend the
(b)(4)
procedure to these said controls.
You have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
4. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Specifically:
A. You either failed to define and document requirements in your Corrective/ Preventive Action Process” procedure (SOP-29, Rev. F, Effective: 10/19/18) or adequately implement sections 5.3, 5.4, and 5.5 which require a “***comprehensive and thorough***” root cause analysis, identification “***of all the actions to prevent recurrence***,” and verification “***that the issue has in fact gone away or been reduced***,” respectively, as required by 21 CFR 820.100(a)(2), 820.100(a)(3), and 820.100(a)(4). For example:
1. Your corrective and preventative action (CAPA) procedure is inadequate in that it does not define or document the requirement to verify or validate corrective actions prior to implementation to ensure they are effective. For CAPA 1175 opened on 11/30/23 for
(b)(4)
blades received with metal debris, leftover burrs, and residue corresponding to
(b)(4)
devices (Part #
(b)(4)
), the corrective actions included (1) increasing clean time to
(b)(4)
minutes for your in-process
(b)(4)
cleaning machines; (2) verifying use of the custom
(b)(4)
fixture; and (3) utilizing additional inspectional tools with both magnification and lighting. However, you did not perform verification or validation activities prior to implementation of the corrective actions to ensure they would be able to remove residue.
2. For CAPA 1175, you failed to adequately implement section 5.3 of your CAPA procedure because your investigation did not include an assessment on whether the residue, caused by improper placement of the devices in the in-process
(b)(4)
machines, may have affected other devices with similar geometries which also use the in-process
(b)(4)
machines to remove residue and metal shards.
3. For CAPA 1166 opened on 7/11/22 to address “staining and contaminants on the
(b)(4)
” on at least
(b)(4)
devices (Part #
(b)(4)
) you contract manufactured under 30 work orders between 1/7/19 to 8/22/22, you failed to implement sections 5.3, 5.4, and 5.5 of your CAPA procedure: (1) investigate the specific causes behind the different types of stains (light stain, glue/transfer, oxidation, dark stain, and material transfer); (2) provide objective evidence that return material authorizations (RMAs) for
(b)(4)
lines were monitored from 3/10/23 to 3/17/23 per the verification plan; and (3) prevent recurrence of this issue in that from 3/17/23 to 4/1/24, you received 7 additional customer complaints/external NCMs (3893; 3902; 3946; 3947; 3980; 3982; and 3984) for stains on at least 7 of the same part numbers (
(b)(4)
) processed under 7 different work orders that were shipped after implementation of the corrective action on 3/10/23.
B. Your “Control of Nonconforming Product” procedure (SOP-33; Rev. P; Eff. 6/28/22), which includes criteria for when corrective and preventive actions (CAPAs) should be initiated, is inadequate in that it does not define and document requirements for analyzing quality data (e.g., complaints, nonconformances, processes, returns, CAPAs, etc.) to identify existing and potential causes of nonconforming product, or other quality problems, using appropriate statistical methodology where necessary to detect recurring quality problems, as required by 21 CFR 820.100(a)(1). For example:
1. Section 6.0 outlines the threshold for when a CAPA should be initiated for a nonconformance report. Threshold categories include Critical to Quality (Score:
(b)(4)
); Rejection % (Score:
(b)(4)
); Occurrence (Score
(b)(4)
); and Detectability (
(b)(4)
). A combined score of
(b)(4)
or above requires initiation of a CAPA. However, your “Detectability” rating does not associate lower ability to detect a nonconformity with a higher risk as a score of
(b)(4)
is defined as “Almost Certain” while a score of
(b)(4)
is defined as “Low to Almost Impossible.” Under this scoring system, recurring quality problems may not be detected because a CAPA would not be initiated for cases where detection was low to almost impossible.
2. Section 5.8.3 states “***the QC Operations Manager***shall review nonconformance data***and determine if trends [for scrapped items, reworked product, nonconforming materials (NCMs)] or significant issue are identifiable and corrective action is warranted***” and that NCM/CAPA meetings will be held periodically to discuss the status of open NCM/CAPAs, trends, and NCM history. However, the procedure does not define and document how you are to analyze internal and external nonconformances as well as other quality data sources (e.g.,
(b)(4)
data) to identify existing and potential causes of nonconforming product, or other quality problems using appropriate statistical methodology.
3. Your nonconformance procedure does not define and document requirements to analyze nonconformances generated from a process that may encompass various part numbers in that your firm’s management stated you only trend nonconformance types by part number. During the inspection, analysis of nonconformances associated with stains between 1/1/20 to 4/1/24 by part number failed to detect a notable trend. When the same data set was analyzed across part numbers, there were 48 nonconformances associated with stains across
(b)(4)
unique part numbers.
4. Your nonconformance procedure does not define and document the nonconformance types (e.g., Major, Manufacturing, GMP, Functional, Dimensional, Gauge etc.), used to categorize nonconformances, to ensure nonconforming product will be consistently assigned a NCM (nonconforming material) type to allow for accurate analysis of this data to identify existing and potential causes of nonconforming product, or other quality problems. For example, NCM # 3458 and NCM # 3469 represent nonconformances associated with devices failing no-go gauges. Employee
(b)(4)
categorized NCM # 3458 as “Dimensional” and the same employee characterized NCM # 3469 as “Guage.” These nonconformances referenced different work orders; however, they each contained identical descriptions, dispositions, and verifications which are specific to the same dimension and no-go gauge.
We reviewed your firm’s response and conclude that it is not adequate.
With regards to CAPA 1175, you plan to investigate the feasibility of the process improvement determined from this CAPA on other product lines. However, there were no corrective actions identified to update your CAPA procedure to include verification or validation of corrective actions prior to implementation.
With regards to CAPA 1166, you explain that staining occurred after product left your firm because you were unable to replicate some of the observed staining; you implemented a 100% visual inspection prior to packaging and shipment and plan to document the visual inspection records for the multiples
(b)(4)
orders verified from 3/10/23 to 3/17/23 as evidence; and you monitored RMAs requests across products lines for
(b)(4)
associated with staining, marks, and contamination from 3/10/23 to 3/17/23 as required by your verification plan. However, none of these conclusions, details, or activities were documented or referenced in your CAPA as part of the investigation, corrective action, and/or verification activities. Overall, there were no corrective actions identified to address the failure to include objective evidence of verification; incomplete documentation of the full investigation, identified corrective actions, and verification plan; and observed recurrence of the issue.
With regards to data analysis, you state you intend to define a final internal nonconforming material (NCM) tracking and trending process within a procedure. However, there were no corrective actions identified to revise the detectability score to ensure that the lowest detectability level equates to the highest score
(b)(4)
not lowest score
(b)(4)
and retrospectively review NCMs, for a reasonable period of time, to update CAPA threshold scores to determine whether any CAPAs should have been initiated.
With regards to categorization of nonconformances, you plan to review and update the existing NCM types listed within the system (as needed); define NCM types; and add instructions on how to correct NCM types after initial entry. However, there were no corrective actions identified to retrospectively review NCM types for accuracy, for a reasonable period of time, to determine the pervasiveness of the issue to guide further corrective action(s) based on the results of the review.
You have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
5. Failure to adequately establish and maintain procedures to control product that does not conform to specified requirements, including the identification, documentation, evaluation, segregation, and disposition of nonconforming product, as required by 21 CFR 820.90(a).
Specifically, your “Control of Nonconforming Product” procedure (SOP-33; Rev. P; Effective: 6/28/22) (nor any other procedure) is inadequate in that there is no requirement to identify, document, and evaluate the following internal nonconformances to determine the need for an investigation. For example:
A.
Internal Nonconformances, found during manufacturing and inspections (excluding
(b)(4)
inspections
– Per your undocumented process, a supervisor logs parts that are out of specification (OOS) into the
(b)(4)
software application and informs your Quality Control (QC) Operations Manager, who in turn enters it on the “Internal NO NCM Issues” log and decides whether to open an official NCM report requiring an investigation per the nonconforming product procedure.
B.
Internal nonconformances, only found during
(b)(4)
inspections conducted during manufacturing
– Per your undocumented process, your QC Operations Manager evaluates the part, approves the disposition of scrap on the inspection guide sheet (IGS), documents it on the “NCM Internal
(b)(4)
Scrap Log” and then discards the part along with the
(b)(4)
report containing the OOS measurement. In turn, your operator enters the scrap on the IGS and
(b)(4)
.
We reviewed your firm’s response and conclude that it is not adequate. There were no actions identified to define and document how internal nonconformances will be evaluated to determine the need for an investigation. Furthermore, you have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
6. Failure to establish and maintain procedures for acceptance activities, including inspections, tests, or other verification activities, as required by 21 CFR 820.80(a).
Specifically, you failed to implement section 6.1.6.1(o) of your “Inspection Process” procedure (SOP-54; Rev. L; Effective: 3/17/23) which states the supervisor (or designate) “***must adhere to the Inspection Frequency as written. If the Inspection Frequency is at an AQL level, the Inspection Frequency is derived from DOC-03 PPI Sampling Plan***.” DOC-3 further references “
(b)(4)
Acceptance Number Sampling Plan Fifth Edition” which requires
(b)(4)
sampling. For example:
A. During in-process inspection of the small spacer intended for implantation during shoulder surgery (Part #
(b)(4)
), your personnel only used your
(b)(4)
to measure the critical diameter feature
(b)(4)
times (to include
(b)(4)
). Per your inspection guide sheet (IGS) for this part, the feature was required to be measured
(b)(4)
times at
(b)(4)
since the inspection plan was specified to follow the Acceptable Quality Limit of
(b)(4)
(AQL
(b)(4)
) defined in “PPI Sampling Plan” (DOC-03; Rev. E; Effective: 12/10/14) for lot sizes of
(b)(4)
and
(b)(4)
under the respective Work Orders (WO) 86995 and 99431, respectively. For WO # 86995, you received a complaint/external nonconformance (NCM # 3287/CAPA 1122) which resulted in
(b)(4)
devices being returned and scrapped due to diameters exceeding the specified limit of
(b)(4)
+/-
(b)(4)
.
B. On 5/17/24, our investigator observed employee
(b)(4)
operate the
(b)(4)
for machining of the metal locking date ring (Part #
(b)(4)
) under WO # 102106. Your operator explained that every
(b)(4)
piece is inspected using a caliper. However, the in-process router states that this operation requires a 100% inspection.
We reviewed your firm’s response and conclude that it is not adequate. You plan to revise the IGS to include column headers and an explanation to record the data for the first setup piece, middle piece, and last piece; review and update the inspection process procedure with the above changes; and provide training on these requirements with an emphasis for operators to follow the specified
(b)(4)
frequency. However, there were no actions identified to determine to determine the pervasiveness of the issue to guide further corrective action(s) based on the results of the review. Furthermore, you have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
7. Failure to adequately establish and maintain schedules for the adjustment, cleaning, and other maintenance of equipment to ensure that manufacturing specifications are met, as required by 21 CFR 820.70(g)(1).
Specifically:
A. Your procedure to define and document the schedule for the
(b)(4)
bowl and filter gauge pressure of the
(b)(4)
Cleaning Machine “
(b)(4)
” (model #
(b)(4)
, serial #
(b)(4)
) is inadequate. The “
(b)(4)
” manual requires drainage and monitoring of the
(b)(4)
volume on a
(b)(4)
basis to prevent liquid from dripping on internal machine components. However, your firm only conducts and documents this maintenance
(b)(4)
on the
(b)(4)
Cleaning System Maintenance Log (Form-03). In addition, although the manual states that the filter gauge pressure should be checked
(b)(4)
and changed if it reaches
(b)(4)
PSI, there is no requirement to check the filter gauge pressure under the “
(b)(4)
” section of your maintenance log (or elsewhere).
B. You do not define, document, and maintain schedules for the adjustment and maintenance of tooling to ensure manufacturing specifications are met. For example, on 4/26/24, our investigator observed an instance where your
(b)(4)
machine was operating with a 0% tool life during the manufacturing of Work Order 101053-1. Per your firm’s management, tool changes may be considered when the machinist deems it necessary based on associated feature measurements, visual checks for a nonconformity on the surface finish of the part, or changes in the tool sound while engaged in the cut. In addition, the machinist may make an adjustment in the tool data page to compensate for the tool wear.
We reviewed your firm’s response and conclude that it is not adequate. As a part of the revalidation of the “
(b)(4)
”, you plan to review the “
(b)(4)
” manual and compare it with the existing preventive maintenance form and update the frequency as needed, and if you determine that a frequency different from what the manual dictates is acceptable, a risk assessment will be performed and documented. You also state that the tooling observation is under review while you consider the best course of action. However, you have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.
8. Failure to adequately establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b).
Specifically, operators who conduct machining of raw materials, assembly, and finishing have not been trained on your “Control of Nonconforming Product” procedure (SOP-33; Rev. P; Effective: 6/28/22). For example, review of 11 training records revealed
(b)(4)
operators who have not been trained in this procedure. These individuals perform in-process inspections and have the ability to reject and accept devices.
We reviewed your firm’s response and conclude that it is not adequate. You plan to update your nonconforming product procedure to include a section for all operators, finishers, and inspectors to state what should be done in the event nonconforming product is found during manufacturing and train all applicable employees to this updated procedure. However, you have not provided any timelines for completion of any of your corrective actions. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review and timelines for completion.
Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm’s response should be sent by email to CDRHWarningLetterResponses@fda.hhs.gov. Refer to CMS Case # 697119 when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, Compliance Offer at (313) 393-8253 or sargum.morgan@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely yours,
/S/
RDML Sean M. Boyd, MPH, USPHS
Director
Office of Regulatory Programs
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Content current as of:
01/14/2025
Regulated Product(s)
Medical Devices