Resubmission Review Email, June 13, 2012 - EVARREST

From:                     Tilghman, Tracy

Sent:                      Wednesday, June 13, 2012 2:54 PM

To:                         'Dauria, Raina [ETHUS]'

Cc:                         Shields, Mark

Subject:                 Reference BL# 125392/0

Dear Ms. Dauria,

 

We are reviewing your March 30, 2012 resubmission for Fibrin Pad to be used as an adjunct to hemostasis for soft tissue bleeding during retroperitoneal, intra-abdominal, pelvic, and (non-cardiac) thoracic surgery when control of bleeding by standard surgical methods of hemostasis is ineffective or impractical.  We request the following information below to continue our review:

 

The responses to the 483 observations that pertain to Fibrin Pad Manufacturing are not adequate and several inspectional issues are not resolved.

 

-(b)(4)-

Observation #4

1.      The response is inadequate as you have not validated the cleaning of all the equipment in use at the facility. For instance:

·         ---------b(4)--------------------------------------------------------------------------------------------------------------------------------

·         -----b(4)---- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

2.   Review of the cleaning validation reports showed that except for very few pieces of equipment, the –b(4)--------------- samples results are typically under –b(4)---- with the vast majority meeting b(4) specification of –b(4)--------.  As per our earlier discussions, you need to set your acceptance criterion to meet your process capabilities which according to your results is way below your acceptance limits of -- -b(4)-.  Please adjust your acceptance limits for –b(4)------ to meet your process capabilities to be in line with –b(4)- specifications.

3.   In the validation reports you stated that you performed -b(4)- sampling to detect b(4).  Please provide the b(4) sampling locations for each of the equipment tested, and justify the selection of each sampling location as a representative (or worst case) to demonstrate the effectiveness of the cleaning procedure.

4.   In the validation reports you set the acceptance criteria for -----b(4)-------------------------------specifications –b(4)-------).  The data provided in the validation reports demonstrate that for the vast majority of equipment the –b(4)--- samples show a much lower –b(4)-------- level.  Please set your acceptance criteria to meet your process capabilities, or justify why you set the limit as –b(4)----- which suggests residual cleaning agent on the equipment. 

5.   In the validation reports, you reported grouping of equipment and performing cleaning validation on a member of the group to demonstrate the validation of the process for the whole group.  However, you failed to list the different groups (and all the items per group), and provide the rationale and justifications for group selection, and that the validation studies were performed on the “worst case” representative of each group using the “worst case” soil.  Please clarify.

6.   You stated that you use –b(4)---------------------------- for the (b)(4) of the different equipment in the different departments.  Please list (in Table format) the ---b(4)------------------- used for the different equipment, and describe each (b)(4) cycle (provide the steps, duration, temperature, volume and concentration of acid and base washes, etc…).

7.   Please provide the frequency of revalidation of the cleaning procedures, and clarify whether you perform regular/periodical or on-line monitoring to assure that the cleaning procedure is effective and within acceptance limits.  Please justify your response.

8.   As a result of the cleaning validation studies, several SOPs were updated to provide for additional –b(4)--------------------------, etc.  Please provide a list of all the SOPs that were updated, and describe the changes incorporated in the latest versions of the SOPs as a result of the validation studies.

9.   You stated that dirty equipment is –b(4)-------------------------------------------------------------------------------------.  Please clarify if this is applicable for all equipment, and if the –b(4)------------------------ is from the –b(4)--------------or from the ---b(4)-----------------------  Please justify your response.

10. You reported the –b(4)---------------------------------------------- for several pieces of equipment.  Please provide the storage conditions/locations to assure that the validated parameters are applicable during routine operations.  Please justify your response.

11. You stated in CLN57 report that –b(4)- validation was “carried out for a portion of the small equipment”; please clarify whether you have a validated –b(4)------------------------------------------------------for all the manufacturing equipment at b(4) and FPPF.  Please justify your response.

12. You described in CLN19 validation report the (b)(4)  procedure where you use                             -------------b(4)----- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

1 page determined to be not releasable: b(4)
