This response letter addresses observations from a warning letter issued by the FDA to XYZ labs on August 15, 2017. It summarizes 3 observations: 1) Failure to properly clean and maintain equipment led to residue issues. Corrective actions included improved training. 2) Failure to follow written recall procedures for a defective product batch until prompted. Personnel were replaced and record handling revised. 3) Failure to thoroughly investigate a customer complaint about a failed dissolution test. Root cause was campaign manufacturing and corrective actions included improved cleaning and training.

1. Response to a warning letter
Submitted by ,
JAYA PRAKASH V,
M.pharmacy 1st year,
Regulatory affairs.

2. About the letter…
 This warning letter was given to the XYZ labs private
limited unit 5 which was located at ABCD region.
 It was a formulation unit.
 Which was issued by the FDA on August 15 2017
 The observations and responses are as follows:

3.  1. Observation :
Your firm failed to clean, maintain, and, as appropriate
for the nature of the drug, sanitize and/or sterilize
equipment and utensils at appropriate intervals to
prevent malfunctions or contamination that would alter
the safety, identity, strength, quality, or purity of the
drug product beyond the official or other established
requirements.

4.  Observation 1(A):
• (b)(4) PDE-2095 had white residue on and around a
white interior gasket.
• Our investigator documented a gap in the gasket that
could allow processed materials to accumulate. The ends
of the gasket were also in poor condition.

5.  Response:
 The white residue on the white interior gasket of (b)(4)
was not the residue. Where they are the water drops after
cleaning , as we placed it for drying .
 Where the gap in the gasket and poor condition of the
gasket of one particular (b)(4) was already kept under
maintenance before your inspections starts .
 where the tag or label not kept by our personnel ,which
your investigator identifies as a defect.

6.  Corrective action:
 By this our firm implemented the training program for
the personnel on proper labeling and tagging to the
equipment which are kept for under maintenance and
incident. And also planned a training program for
personnel who are involved in the cleaning activity.

7.  Observation 1(B):
Our investigators observed multiple (b)(4), which you
identified as clean, containing colored residue and/or in
poor condition.

8.  Response:
 As the colored residue on the (b)(4) found in your
observation was sampled and analyzed to identify and
quantify any chemical and microbiological
contaminants.
 And the results met microbial contaminants.
 As our team investigated the root cause for the colored
residue on the cleaned (b)(4) .
 It was finally found that the residue is due to improper
cleaning of that particular multiple (b)(4) by our
personnel ,which was only found in the block-5 and
block-6 of manufacturing area.

9.  Corrective action:
 By this observation our firm implementing proper
training plan to the personnel responsible for cleaning,
verifying equipment cleanliness, and maintaining
equipment.
 which is capable of performing their assigned duties.
Include cleaning validation was done.
 And also we are implementing self inspection program
to evaluate and minimize the defects.

10.  2.Observation:
 Your firm failed to establish adequate written
responsibilities and procedures applicable to the quality
control unit and to follow such written procedures.
 Your firm’s procedures, QM001-04 Quality System
Manual and CQA012-01 Product Recall, direct your
firm to recall products , but your quality control unit
failed to follow your written procedures regarding the
recall of failing product.

11.  On July 8, 2016, you received a complaint that one
tablet in a bottle of 5 mg finasteride tablets, lot
FIN16002, was approximately double the thickness of
the others. You confirmed the defect after receiving the
complaint sample on July 27, 2016, but did not initiate a
product recall as directed by your own procedures until
investigators pointed out.

12.  Response:
 As our firm has an efficient quality system manual and
product recall procedure.
 But distribution record for that particular product was
destroyed along with the expiry products distribution
records.
 Which this happens because of the misplacing of the
distribution records of that product by our personnel

13.  Corrective action:
 Where the personnel involved in this activity have been
removed from our firm.
 We implemented the training program for the personnel
responsible for storing, archiving ,destroying of the
distribution records.
 And revising the sops , how to handle the distribution
records.

14.  3.Observation
 Your firm failed to thoroughly investigate failure of a
batch or any of its components to meet any of its
specifications, whether or not the batch has already been
distributed.
 For example, you have acted as the contract
manufacturer of (b)(4) mg (b)(4) tablets for multiple
customers. In February 2017, you received a customer
complaint that lot (b)(4) failed dissolution testing.

15.  Response :
 We thoroughly investigate the batch failure of (b)(4) by
root cause analysis on your observation.
 The cause for the batch failure was due to the campaign
manufacturing.
 Corrective action:
 We are implemented the duration time for manufacturing
and proper cleaning procedures.
 And proper training program for the personnel in
manufacturing and cleaning personnel.

16. THANK U