Customed, Inc 12/9/14

Public Health Service

Food and Drug
Department of Health and Human Services
Administration
Compliance Branch
466 Fernández Juncos
Avenue
San Juan, Puerto Rico
00901-3223
Telephone: (787) 729-8500
Fax: (787) 729-8765

December 9, 2014

WARNING LETTER
15-SJN-WL-01

HAND DELIVERED

Mr. Felix B. Santos

President and Owner
Customed Inc.
Calle Igualdad Final #7
Fajardo, Puerto Rico 00738

Dear Mr. Santos:

During an inspection of your firm, Customed Inc., located at Calle Igualdad Final #7,
Fajardo, Puerto Rico on July 14 through July 31, 2014, investigators from the United
States Food and Drug Administration (FDA) determined that your firm is a manufacturer of
medical devices, including convenience packs for surgical procedures. 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 are
intended to affect the structure or function of the body.

This inspection disclosed 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 (CGMP) requirements of the Quality
System Regulation (QSR) found in Title 21, Code of Federal Regulations (C.F.R.), Part
820.

We acknowledge receipt of your firm’s response on August 21, 2014, from Mr. Hector
Agosto, General Manager and a response update on September 8, 2014. These
documents address the observations noted on Form FDA 483, List of Inspectional
Observations that was issued at the closing of our inspection on July 31, 2014. The
document was issued to Mr. Hector Agosto; however, you participated in the closing
meeting via conference call. We address your responses below, in relation to each of the
noted violations.

The QSR violations include, but are not limited to, the following:

1. Failure to validate with a high degree of assurance, a process which results cannot be
fully verified by subsequent inspection and test, as required by 21 CFR Part
820.75(a). According to your firm’s documentation, the re-qualification of the Ethylene
Oxide (EtO) Sterilization Cycle (b)(4) Protocol and Report (b)(4) and REV (b)(4), dated
05/10/2013 and 06/05/2013 respectively), was performed according to (b)(4) to qualify the
terminal sterilization of the medical device/convenience kits. Per (b)(4), the sterilization of
your convenience kits is deficient because Protocol and Report (b)(4) and (b)(4) does not
demonstrate that critical factors were adequately considered. For example:

a. Your firm did not perform post-sterilization inspection as part of the performance
re-qualification study to determine if the sterilization process adversely impacted product
functionality and packaging integrity. According to the “Process Re-Qualification for
Customed Soft Cycle”, Final Report # (b)(4), dated 06/05/2013, “No physical inspection
was conducted (b)(4) product.”

b. SOP (b)(4), “Esterilización por Oxido de Etileno” (translation: EtO Sterilization),

allows the load configuration to be sterilized to contain different convenience packs,
combined (b)(4). The Process Re-qualification for Customed Soft Cycle Validation
documents (Protocol and Report (b)(4) and (b)(4), dated 05/10/2013 and 06/05/2013,
state “The products selected represent a reference load selection for actual Customed
product”. There is no justification to support:

i. Product packages used during the Process Qualification (b)(4) sterilize product
package configurations (b)(4);

ii. The load type and load configuration used during the Process Qualification
represent (b)(4)

c. Your firm has provided installation and operational qualification protocols for (b)(4).
The data provided appears to contain factual errors such as, (b)(4). Therefore, it’s not
possible to effectively determine whether the data provided is sufficient to support
the (b)(4) qualification and sealing process validation.

We reviewed your firm’s response dated August 21, 2014, and it’s not adequate. While
your firm initiated Corrective Action and Preventive Action (CAPA) (b)(4) to perform an
EtO sterilization Soft Cycle (b)(4) and committed to generate a protocol that follows the
new Revision of ISO 11135: (R) 2014, your firm’s response is deficient, because it failed
to address each of these issues and it’s unclear whether the protocol was developed and
fully implemented, and which requirements from ISO 11135 will be in the new
requalification protocol. The corrective action does not describe the specific sterilization
process that will be used to sterilize medical devices and kits after requalification of the
EtO Sterilization Soft cycle. In addition, the corrective action does not describe how the
sterilization cycles are validated and revalidated to ensure a Sterility Assurance Level
(SAL) (b)(4). We reviewed your firm’s response and conclude that it is not adequate. Your
firm’s response dated August 21, 2014, did not address item “c”.

2. Failure to establish and maintain procedures for implementing corrective and

preventive action, as required by 21 CFR 820.100(a). Your firm has not implemented and
recorded corrective actions needed to correct and prevent identified quality problems. For
example, CAPA (b)(4) was opened after receiving complaint (b)(4) related to saline
bottles contained within the (b)(4). Your firm determined that a suitable alternative was
required as substitute item. However, your firm did not identify a corrective action to
retrospectively review all components subjected to Customed sterilization cycle to
determine suitability and compatibility with the sterilization cycle parameters. Your firm’s
response dated August 21, 2014, did not address this concern.

3. Failure to maintain records of an investigation made under 21 CFR 820.198, as

required by 21 CFR 820.198(e). For example:

a. The individual observing the alleged device defect (i.e. physician/nurse/end-user)

was not recorded in the following complaint numbers: (b)(4), and (b)(4).

b. The specific details of the reported incident were not recorded, including, whether the
device was being used for treatment or diagnosis and any adverse consequences to the
end-user was not recorded in the following complaint numbers: (b)(4), and (b)(4).

Your firm’s response dated August 21, 2014, is not adequate. Your firm initiated
CAPA (b)(4), but failed to provide for review the revised Complaint Handling
Procedure, (b)(4), and evidence of its implementation, such as training records,
documentation of complaints initiated, handled and investigated under the revised
procedures. Further, it appears that your firm did not consider performing a retrospective
review of complaint investigations to determine if information was properly recorded or
missing, or if an additional corrective action was required.
4. Failure to validate the defined user needs and intended uses of the (b)(4) used as
part of the quality system according to an established protocol, as required by 21 CFR
820.70(i). Specifically, your firm implemented (b)(4) to track product inventory (incoming
materials, finished/released products and quarantine items), however the software was
not validated. In addition, the status of lots of finished products and incoming materials in
the warehouse failed to match the (b)(4) system inventory.

Your firm’s response dated August 21, 2014, is not adequate. Your firm initiated
CAPA (b)(4) to prepare a software validation protocol, however, you failed to initiate a
corrective action to identify and address pertinent quality system and production software
that have not been appropriately validated. Further, your firm failed to provide the
executed (b)(4) validation protocol and summary report for review.

5. Failure to ensure that device packaging and shipping containers are designed and
constructed to protect the device from alteration or damage during the customary
conditions of processing, storage, handling, and distribution, as required by 21 CFR
820.130. For example, your firm has not adequately demonstrated that the terminally
sterile medical packaging and product can withstand the rigors of transit, handling and
storage environments without compromising the sterility of the pack, product features and
performance. Your firm provided shipping validation documents conducted June 2006 that
included products packaged in trays or breather bags including convenience packs
intended for cardiovascular and ophthalmic surgeries. Review of the shipping validation
protocol demonstrated that your firm performed EtO validation using the outside
cardboard shipping containers in June 2006, but did not perform validation of the inside
convenience packages after the EtO Sterilization process in order to verify the integrity of
the packages.

Your firm’s response dated August 21, 2014, is not adequate. Your firm committed
to (b)(4) products; however, it was found deficient because you did not consider the
stability or shelf life of the sterile barrier that the devices and kits are packaged in.
Additionally, packaging and shipping validation protocols, describing the testing to be
performed to demonstrate the sterility and stability of the packaged device was not
compromised after manufacturing and distribution, were not submitted including a timeline
for implementation of corrective and preventive measures.

6. Failure to establish and maintain requirements for the health, cleanliness, personal
practices, and clothing of personnel if contact between such personnel and product or
environment could reasonably be expected to have an adverse effect on product quality,
as required by 21 CFR 820.70(d). For example, your firm did not establish gowning
requirements for the manufacture of finished product to minimize bioburden or particulate
contamination of the device. Employees were observed assembling sterile and non-sterile
convenience kits without gloves.
Your firm’s response dated August 21, 2014, is not adequate. Your firm initiated
CAPA (b)(4) and committed to utilize an external resource to conduct a manufacturing
evaluation to determine additional controls for employee gowning, product handling and
environmental controls, however the CAPA failed to identify and provide an immediate
interim correction that addresses bioburden and particulate concerns of sterile and
non-sterile convenience kits. Additionally, your firm has not provided evidence of the
additional controls identified by your external resource or the implementation of such
proposed corrective actions.

7. Failure to establish and maintain procedures for the control of storage areas and
stock rooms for products to prevent mix-ups, damage, deterioration, contamination or
other adverse effects pending use or distribution and to ensure that no obsolete, rejected,
or deteriorated product is used or distributed, as required by 21 CFR 820.150(a). For
example:

The finished goods warehouse had:

 stored expired products that were not segregated from stored finished products ready
for distribution,

 black and brown stains that appeared to be mold on a wall and ceiling in the finished
products area,

 open windows and doors, without screens to protect against entry of pests.
The incoming and raw material warehouse had:
 product without expiration dates that showed visible signs of deterioration,

 discontinued items still available in inventory,

 open windows and doors, without screens to protect against entry of pests.
Your firm’s response dated August 21, 2014, is not adequate. Your firm initiated
CAPA (b)(4) on April 08, 2014, following an internal audit observation to address material
review board and quarantine area congestion as well as untimely nonconforming product
disposition. However, the additional action items that were added to the corrective action
plan during the inspection were not adequate.

For example:
 No evidence has been provided to show that protective screens or nets have been
installed in the incoming and finished goods warehouses. There is no evidence that
screens/nets have been installed in the loading/unloading docks. In addition, the above
CAPA does not state if glass in “open” or unshielded windows has been replaced;

 Your firm committed to creating an SOP for warehouse cleaning and maintenance;
however, there is no evidence that cleaning of the walls, ceiling, and shelving to
remove visible mold and dust has been performed or scheduled;

 No evidence has been provided to show that repair of water leaks in the ceiling and
along the wall, resulting in the presence of mold, has been performed or scheduled.
Additionally, your firm failed to provide evidence that deteriorated, damaged, discontinued,
and expired products were removed from active inventory. Further, your firm has not
completed and submitted evidence of implementation of its identified corrective actions, to
include but not limited to, new/revised SOPs, to prevent mix-ups, and to assure orderly
handling.

Our inspection also demonstrated that the sterile/non-sterile convenience kits are
misbranded under Section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm
failed or refused to furnish material or information regarding the devices required by
Section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting
(MDR).

Significant MDR deviations include, but are not limited to:

Failure to adequately develop, maintain and implement written MDR procedures, as

required by 21 CFR 803.17. We reviewed your firm’s MDR procedure titled “Complaint
Handling Procedure SOP (b)(4)”, dated 4/14/2010, and “MDR Analysis (b)(4)”. Both
documents were collectively considered as your firm’s MDR procedure.

After reviewing your firm’s MDR procedure, the following deviations were noted:

8. The procedure does not establish internal systems that provide for timely and
effective identification, communication, and evaluation of events that may be subject to
MDR requirements. For example:

a. The procedure does not include definitions for the terms: “become aware,” “caused or
contributed,” “malfunction,” “MDR reportable event,” and “serious injury,” found in 21 CFR
803.3, and the definition for the term “reasonably suggests”, found in CFR 803.20(c)(1).
The exclusion of the definitions for these terms from the procedure may lead your firm to
make an incorrect reportability decision when evaluating a complaint that may meet the
criteria for reporting under 21 CFR 803.50(a).

9. The procedure does not establish internal systems that provide for timely
transmission of complete medical device reports. Specifically, the following are not
addressed:

a. The procedure does not include or refer to instructions on how to obtain and
complete the FDA 3500A Form.

b. The circumstances under which your firm must submit initial 30 day, supplemental or
follow-up, and 5 day reports and the requirements for such reports.

c. The procedure does not include the address for where to submit MDR reports: FDA,
CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
10. The procedure does not describe how your firm will address documentation and
record- keeping requirements, including:

a. Documentation of adverse event related information maintained as MDR event files;

b. Information that was evaluated to determine if an event was reportable;

c. Documentation of the deliberations and decision-making processes used to

determine if a device-related death, serious injury, or malfunction was or was not
reportable;

d. Systems that ensure access to information that facilitates timely follow-up and
inspection by FDA.

The adequacy of your firm’s response dated August 21, 2014, cannot be determined at
this time. Your firm’s response states that corrective actions are planned and will be
implemented in September and October of 2014. However, until we receive evidence that
the changes were implemented, we cannot make an assessment with respect to
adequacy.

The eMDR Final Rule requiring manufacturers and importers to submit electronic Medical
Device Reports (eMDRs) to FDA was published on February 13, 2014. The requirements
of this final rule will take effect on August 14, 2015. If your firm is not currently submitting
reports electronically, we encourage you to visit the following web link for additional
information about the electronic reporting
requirements: http://www.fda.gov/ForIndustry/FDAeSubmitter/ucm107903.htm

If your firm wishes to discuss MDR reportability criteria or to schedule further

communications, it may contact the Reportability Review Team by email
at ReportabilityReviewTeam@fda.hhs.gov

Premarket Approval (PMA)

Our review of the Laparotomy packs demonstrated that Customed Inc. manufactures
Laparotomy packs with device components (b)(4). These device components are Class
II devices under 21 CFR 878.4400, and require a premarket notification unless one or
more of the following conditions are met: (1) the component is a legally marketed
preamendment device, (2) the component is exempt from premarket notification, or (3) the
component has been found to be substantially equivalent through the premarket
notification process. Your firm did not provide enough information for FDA to determine if
any of those conditions apply.
Your Laparotomy packs are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. §
351(f)(1)(B), because your firm does not have an approved application for premarket
approval (PMA) in effect pursuant to Section 515(a) of the Act, 21 U.S.C. § 360e(a), or an
approved application for an investigational device exemption (IDE) under Section 520(g)
of the Act, 21 U.S.C. § 360j(g). The device is also misbranded under Section 502(o) the
Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to
introduce the device into commercial distribution, as required by Section 510(k) of the Act,
21 U.S.C. § 360(k) and the devices did not meet the exception under 21 CFR
807.81(b)(1).

Under Section 510 of the Act (21 U.S.C. § 360), manufacturers of medical devices are
required to annually register with the FDA. In September 2007, Section 510 of the Act was
amended by the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85)
to require domestic and foreign device establishments to submit their annual
establishment registration and device listing information to FDA by electronic means
[Section 510(p) of the Act (21 U.S.C. § 360(p))] during the period beginning October
1st and ending December 31st of each year. Our records indicate that your firm has not
fulfilled annual registration and listing requirements for fiscal year 2014.

Therefore, all of your firm’s devices are misbranded within the meaning of Section 502(o)
of the Act (21 U.S.C. § 352(0)), in that the devices were manufactured, prepared,
propagated, compounded, or processed in an establishment not duly registered under
Section 510 of the Act (21 U.S.C. § 360) and were not included in a list required by
Section 510(j) of the Act (21 U.S.C. § 360(j)).

You should take prompt action to correct the violations addressed in this letter. Failure to
promptly correct these violations may result in regulatory action being initiated by the
Food and Drug Administration without further notice. These actions include, but are not
limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are
advised of the issuance of all Warning Letters about devices so that they may take this
information into account when considering the award of contracts. Additionally, premarket
approval applications for Class III devices to which the Quality System Regulation
deviations are reasonably related will not be approved until the violations have been
corrected. Requests for Certificates to Foreign Governments will not be granted until the
violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) business days from the date you
receive this letter of the specific steps your firm has taken to correct 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 all violations included in this Warning Letter.

Your firm’s response should be sent to: Director of Compliance Branch, Mr. Edwin Ramos,
Food and Drug Administration, San Juan District Office, 466 Fernandez Juncos, San Juan,
Puerto Rico 00901. Refer to the Unique Identification Number CMS case # 440230 when
replying. If you have any questions about the contents of this letter, please contact: Mrs.
Marilyn Santiago, Compliance Officer at (787) 729-8707 or
email Marilyn.santiago@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
the violations, and take prompt actions to correct the violations and bring the products into
compliance.

Sincerely yours,
/S/
Edwin Ramos
Director of Compliance Branch
San Juan District Office
Close Out Letter
 Customed, Inc - Close Out Letter 12/14/16