Note: Although this FDA-483 is an
accurate representation of the original FDA-483 issued to the firm, it is not an exact
copy. Slight modifications to the original FDA-483 have been made to accommodate its
conversion to the HTML format. A scanned copy of the original FDA-483 is available in PDF format on this website. |
DEPARTMENT
OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION |
DISTRICT
OFFICE ADDRESS AND PHONE NUMBER
60 Eighth Street NE
Atlanta, GA 30309
(404) 253-1161 Fax:(404) 253-1202
|
DATE(S)
OF INSPECTION
03/22/2006 - 05/15/2006 |
FEI
NUMBER 1032500 |
NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO: Mr.
Thomas H. Eggleton, VP of Operations |
FIRM
NAME
Bausch & Lomb Inc. |
STREET
ADDRESS
8507 Pelham Rd |
CITY,
STATE AND ZIP CODE
Greenville, SC 29615-9598 |
TYPE
OF ESTABLISHMENT INSPECTED
Medical Device/Pharmaceutical Manufacturer
|
This document lists
observations made by the FDA representative(s) during the inspection
of your facility. They are inspectional observations, and do not
represent a final Agency determination regarding your compliance.
If you have an objection regarding an observation, or have implemented,
or plan to implement, corrective action in response to an observation,
you may discuss the objection or action with the FDA representative(s)
during the inspection or submit this information to FDA at the address
above. If you have any questions, please contact FDA at the phone
number and address above. |
The observations
noted in this Form FDA-483 are not an exhaustive listing of objectionable
conditions. Under the law, your firm is responsible for conducting
internal self-audits to identify and correct any and all violations
of the quality system requirements. |
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: |
OBSERVATION 1
The design plan does not describe the design and development activities,
define responsibility for implementation of design and development
activities, and identify and describe the interfaces with other
groups or activities as appropriate.
MEDICAL DEVICE REGULATIONS
Specifically, a complete design plan was not done for ReNu w/ MoistureLoc
Multi-Purpose Solution. The plan provided is incomplete and does
not provide clear traceability through the design project. For example:
-
The initial design plan shows Project [REDACTION] began in 2001
and resulted in product [REDACTION]. The formulation contains
a different preservative [REDACTION] and was cleared by the
Agency in 2003. The product was not commercialized by the firm.
Project [REDACTION] is an alternate product project [REDACTION],
ReNu w/ MoistureLoc Multi-Purpose Solution containing Alexidine,
which was added to the same original design and development
plan in 2004. Initial feasibility and risk assessment show the
two products with two perservative agents ([REDACTION] and Alexidine)
under one design project.
-
Raw material specifications were not determined and firmly
established prior to process validation. For example, [REDACTION]
was used for pre-clinical and clinincal studies however, the
product formulation was changed to [REDACTION] at initial validation
then back to [REDACTION].
-
Tasks for determining analytical in-process and finished product
specifications were not assigned in the design plan and they
were not firmly established prior to the product launch of ReNu
w/MoistureLoc Multipurpose Solution. For example, [REDACTION]
release specification was lowered after beginning process validation.
-
The firm does not have a test method to evaluate the degradation
of Alexidine in the ReNu w/MoistureLoc Multipurpose Solution.
-
The design history file does not contain a statement of readiness
from R&D as required in established procedure BL POL-401,
Product Development Management Process.
|
OBSERVATION 2 Design input requirements that
are incomplete were not addressed.
Specifically, several design inputs for ReNu w/ MoistureLoc Multi-Purpose
Solution [REDACTION] are outstanding and were not addressed by the
project team before bringing the product to the market. For example,
the following value added design inputs remain open: qualification
of a no rub, no rinse regimen for the CE Mark; [REDACTION]of cycled
lenses ([REDACTION] cycles) with Group 1-4 lenses (no rub, no rinse);
ISO/FDA Regimen Test using [REDACTION] and [REDACTION] after a [REDACTION]
hour and [REDACTION] day soak in glass vials; laboratory cleaning
study to demonstrate lipid removal with [REDACTION] lenses; and,
a biocidal efficacy study that demonstrates efficacy against "clinically
significant microorganisms" (non-ISO organisms).
|
OBSERVATION 3 Design reviews were
not performed at appropriate times, following the review schedule.
Specifically, the post-launch product review for the ReNu w/ MoistureLoc
Multi-Purpose Solution has not been performed as required in the
formally established procedures, BL-PRO-408, Project Post Launch
Review. The review should occur during the first year after the
product is launched. ReNu w/MoistureLoc Multi-Purpose Solution was
initially distributed from the Greenville site in August 2004. [REDACTION].
|
OBSERVATION 4 An MDR report was not
submitted within 30 days of receiving or otherwise becoming aware
of information that reasonably suggests that a marketed device may
have caused or contributed to a death or serious injury.
Specifically,
-
The firm failed to notify the Agency of 35 serious injury reports
of Fusarium Keratitis from Singapore's Minister of Health in
February 2006 relating to ReNu MoistureLoc Multi-Purpose Solution.
None of the complaints were reported to the Agency as of April
7, 2006.
-
Complaint #S105000240 - #S105000245 were initially reported
to the firm as Keratitis complaints in July 2005. These complaints
have not been reported to the Agency as of May 9, 2006.
-
Complaint # S105000012 was initially reported as a chemical
burn, but was later updated as Keratitis. The complaint has
not been reported as an MDR.
|
OBSERVATION 5 A correction or removal,
conducted to reduce a risk to health posed by a device, was not
reported in writing to FDA.
Specifically, the firm failed to report the removal of ReNu MoistureLoc
Multi-Purpose Solution from the market in Singapore and Hong Kong
in February 2006.
|
OBSERVATION 6
A validated process was not revalidated when changes or process
deviations occurred.
Regarding the validation of ReNu w/ MoistureLoc Multi-Purpose Solution:
-
The firm does not have complete validation data for ReNu w/
MoistureLoc Multi-Purpose Solution [REDACTION]. Initial scale-up
activities at the Greenville plant were performed in 2003 on
an unnamed similar product [REDACTION] utilizing [REDACTION]
in the product formulation. [REDACTION] replaced [REDACTION]
(which was used in the original product formulation for pre-clinical
and clinical studies) after white particles were noted on soft
contact lens while performing a lens compatibility study. The
[REDACTION] product was formulated with [REDACTION] and used
in the validation study; however, the formulation was not commercialized.
In 2004 the firm performed a limited validation study on the
currently marketed Renu w/ MoistureLoc Multi-Purpose Solution
utilizing [REDACTION] in the product formulation. The corrective
action to avoid the appearance of white particles on the lenses
was to use the [REDACTION], USP with a European Pharmacopeia
clarity test. The validation data available shows that cleaning
of the bulk mix tanks and filling lines, the filling process,
the hold time study, and purging processes were not re-validated.
Chemistry testing was limited to the compounding batches and
no USP sterility testing was performed for the scaled-up batches
of ReNu w/MoistureLoc Multi-Purpose Solution. [REDACTION] validation
data was accepted in lieu of performing a complete re-validation
of the manufacturing processes.
-
The following deviations are noted in the initial validation
study [REDACTION]:
-
The European Pharmacopeia (EP) clarity test was not performed
on Lot # 234068 [REDACTION]) that was used in the 2003 validation
study. Raw material specifications included a requirement
for the EP clarity test in 2003.
-
Bacteriostasis/Fungistasis (B/F) testing was not performed
for all validation runs as specified in the established protocol
(0308-ME-0154). [REDACTION] runs were performed; however B/F
testing was performed on only one run.
-
The first bottle out of filling on the [REDACTION] batch
([REDACTION]) was out of specification on the lower end for
[REDACTION]. At the time of fill the release specifications
were [REDACTION]. The release specifications were subsequently
lowered to [REDACTION] and this run was accepted.
|
OBSERVATION 7
Procedures have not been followed to prevent contamination of equipment
or product by certain substances.
Specifically,
-
On 4/19/06 in the upper mix room, peeling paint and paint
chips were observed on agitators located on the tops of tank
#[REDACTION]and the solenoid above tank #[REDACTION]. These
tanks are currently used for the production of contact lens
solutions.
-
The cleaning, inspection, and sanitization of fill lines #[REDACTION]used
in the production of [REDACTION], Sensitive Eyes, Boston Cleaner,
ReNu w/Moisture Loc Multi-Purpose Solution were not documented
as per SOP #40-102-19, "Weekly and Monthly Cleaning and
Inspection of APA", for the monthly cleaning conducted
for the month of February 2006.
|
OBSERVATION 8
Appropriate procedures have not been defined and documented for
controlling environmental conditions.
Specifically,
Temperature conditions within the aseptic processing area are not
being documented to ensure such conditions are consistently within
established specifications of [REDACTION] degrees Celsius.
|
OBSERVATION 9
Complaints involving the possible failure of a device to meet any
of its specifications were not investigated where necessary.
Specifically as of 3/23/06
-
The Fusarium Keratitis investigation did not include sterility
or biocidal testing for ReNu w/ MoistureLoc Multi-Purpose Solution
product lots implicated in complaints received from Hong Kong.
-
The firm had not performed sterility testing on the return/retain
samples in conjunction with the Fusarium investigation for complaints
received from Malaysia and Singapore.
|
OBSERVATION 10
Procedures for controlling the storage of product in storage areas
and stock rooms were not implemented to prevent mix-ups, damage,
other adverse effects.
Specifically,
-
On 4/4/06 the firm failed to locate a product lot implicated
in a customer complaint, ReNu w/ MoistureLoc Multi-Purpose Solution,
Lot# GG5055, which was identified as being part of the current
inventory in the firm's validated inventory control systems
[REDACTION].
-
On 4/24/06 the firm was unable to locate [REDACTION] cases
of ReNu MoistureLoc Multipurpose Solution, Lot #AJ5065.
-
On 5/9/06 the firm was unable to locate [REDACTION] units
of ReNu MultiPlus Multipurpose Solution, Lot #GC6061.
|
OBSERVATION 11
Quality audits were not conducted to verify that the quality system
is effective in fulfilling your quality system objectives.
Specifically,
-
Review of the Internal Audit schedule indicated that the firm
has not conducted or established a routine auditing of their
complaint handling system.
-
The firm does not have procedures defining the frequency by
which supplier audits will be conducted.
-
The firm has never audited the supplier of [REDACTION], a
component used to manufacture ReNu w/ MoistureLoc Multi-Purpose
Solution.
-
Contract laboratories/suppliers used in raw material and finished
product testing have not been audited at a defined frequency.
For example:
- Lab A was last audited on 12/11/98
- Supplier A was last audited on 9/11/01
In addition, the last biennial audit of Lab B was conducted
on 12/3/2003.
|
OBSERVATION 12
Procedures have not been implemented to ensure that mix-ups, damage,
or other adverse effects to product do not occur during handling.
Specifically,
-
No documentation, inspection, audit, or checklist were established
or conducted to guarantee that the trucking company transporting
finished product from the manufacturing plant to the distribution
center is protecting materials and finished product from damage
and contamination as specified in SOP #15-006-09. Additionally,
the trucking company does not have a climate control system
in the trailer to monitor temperature conditions.
-
There are no procedures indicating the amount of time finished
products are allowed to remain stored in trailers before finding
a location in the warehouse for storage.
|
OBSERVATION 13
Appropriate design, construction, placement, and installation of
manufacturing equipment have not been ensured.
Specifically,
On 3/27/06 clean, uncapped product transfer hoses that are used
in production were observed in direct contact with a shelving unit
upon which a visible layer of a white powdery residue was observed.
The shelving unit was installed to prevent hoses from coming in
contact with the manufacturing room floor.
|
OBSERVATION 14
Maintenance activities, including the date and individuals performing
those activities, have not been documented.
FINISHED PHARMACEUTICALS
Specifically, integrity testing of the vent filters on the [REDACTION]
Hot Purified Water (HPW) tanks was not conducted during the [REDACTION]
month interval between June 2005 and March 2006 per SOP # 50-095-08.
|
OBSERVATION 15
Written procedures are not followed for the cleaning and maintenance
of equipment, including utensils, used in the manufacture, processing,
packing or holding of a drug product.
Specifically,
Your established mix tank cleaning procedures, SOP# 40-017 entitled,
"Clean In place System for Mix Tanks", require specific
manual cleaning procedures for [REDACTION] that include a [REDACTION]
minute manual rinse at [REDACTION] degrees Celsius, prior to the
automated CIP cycle. Review of batch record documentation and cleaning
cycle records found that this manual rinse is not being documented.
|
OBSERVATION 16
The written stability program for drug products does not include
meaningful and specific test methods.
Specifically,
The current analytical test methods for OTC drug products are not
stability-indicating to demonstrate levels of degradation or other
impurities that may exist in such products.
|
OBSERVATION 17
Employees are not given training in the particular operations they
perform as part of their function.
Specifically, [REDACTION] of the [REDACTION] operators within [REDACTION]
operations have not participated in [REDACTION] media fills, as
per SOP# 90-161-02, "Validation of Aseptic Fill Challenges",
to ensure the operators remain current with relevant established
procedures and cGMPs. |
OBSERVATION 18
There are no written procedures for production and process controls
designed to assure that the drug products have the identity, strength,
quality, and purity they purport or are represented to possess.
Specifically, there are no specific established procedures for
the visual examinations of incubated vials conducted by microbiological
technicians during media fill operations.
|
FDA EMPLOYEE'S NAME, TITLE, AND SIGNATURE:
[signature]
Claudette D. Brooks, Investigator
[signature]
Babatunde D. Babalola, Investigator
[signature]
Bonita S. Chester, Investigator |
SEE
REVERSE
OF THIS
PAGE |
|
|
DATE
ISSUED 05/15/2006 |
DEPARTMENT
OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION |
DISTRICT
OFFICE ADDRESS AND PHONE NUMBER
60 Eighth Street NE
Atlanta, GA 30309
(404) 253-1161 Fax:(404) 253-1202
|
DATE(S)
OF INSPECTION 03/22/2006 -
05/15/2006 |
FEI
NUMBER 1051854 |
NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO: Mr.
Thomas H. Eggleton, VP of Operations |
FIRM
NAME
Bausch & Lomb Inc. |
STREET
ADDRESS
130 Commerce Ctr |
CITY,
STATE AND ZIP CODE
Greenville, SC 29615-5816 |
TYPE
OF ESTABLISHMENT INSPECTED
Repackager/Relabeler |
This document lists
observations made by the FDA representative(s) during the inspection
of your facility. They are inspectional observations, and do not
represent a final Agency determination regarding your compliance.
If you have an objection regarding an observation, or have implemented,
or plan to implement, corrective action in response to an observation,
you may discuss the objection or action with the FDA representative(s)
during the inspection or submit this information to FDA at the address
above. If you have any questions, please contact FDA at the phone
number and address above. |
The observations
noted in this Form FDA-483 are not an exhaustive listing of objectionable
conditions. Under the law, your firm is responsible for conducting
internal self-audits to identify and correct any and all violations
of the quality system requirements. |
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: |
OBSERVATION 1
Procedures for controlling the storage of product in storage areas
and stock rooms were not established to prevent mix-ups, damage,
other adverse effects.
Specifically, the firm does not monitor the temperature of the
storage warehouse at the distribution center, although product labeling
specifies that products should be stored at room temperature. For
example, ReNu w/ MoistureLoc Multi-Purpose Solution and ReNu Multiplus
Multi-Purpose Solution.
|
OBSERVATION 2 Procedures have not been documented
to prevent contamination of equipment or product by certain substances.
Specifically, the firm does not have established procedures or
practices for cleaning the packaging areas or packaging equipment
in the distribution center. On 3/22/06 Boston Convenience Packs,
Lot # AC6050 were being packaged on Line #[REDACTION]. Twelve (12)
oz ReNu w/ MoistureLoc Multi-Purpose Solution twin packs with 2
oz. ReNu w/ MoistureLoc, Lot #AC6035 was also being packaged on
Line # [REDACTION]. The packaging equipment including the equipment
coverings, on both lines was dirty and dusty. Additionally, the
entire packaging area was in need of cleaning.
——
Annotation: Reported corrected, not verified.
|
FDA EMPLOYEE'S NAME, TITLE, AND SIGNATURE:
[signature]
Claudette D. Brooks, Investigator
[signature]
Babatunde D. Babalola, Investigator
[signature]
Bonita S. Chester, Investigator |
SEE
REVERSE
OF THIS
PAGE |
|
|
DATE
ISSUED 05/15/2006 |
FORM
FDA 483 (7/00) PREVIOUS EDITION OBSOLETE
INSPECTIONAL
OBSERVATIONS
Reverse Text on Page: The observations of objectional conditions and practices listed
on the front of this form are reported:
- Pursuant to Section 704(b) of the Federal Food, Drug and
Cosmetic Act, or
- To assist firms inspected in complying with the Acts and
regulations enforced by the Food and Drug Administration.
|
Section 704(b) of the Federal Food, Drug, and Cosmetic
Act (21 USC374(b)) provides: “Upon
completion of any such inspection of a factory, warehouse, consulting laboratory, or other
establishment, and prior to leaving the premises, the officer or employee making the
inspection shall give to the owner, operator, or agent in charge a report in writing
setting forth any conditions or practices observed by him which, in his judgement,
indicate that any food, drug, device, cosmetic in such establishment (1) consists in whole
or in part of any filthy, putrid, or decomposed substance or (2) has been prepared,
packed, or held under insanitary conditions whereby it may have become contaminated with
filth, or whereby it may have been rendered injurious to health. A copy of such report
shall be sent promptly to the Secretary.” |
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