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Sl # Observations Action Status

Premises and equipment are not maintained properly as


cleanliness is not satisfactory to suit the operations to be
1.
carried out. (Major) (Clause: point 3.1, 3.2, 3.9, 3.10, 3.15
and 5.18 SFDA guideline).
Most of all walls in production were not smooth and not easy
1.1. Walls and sharp edges, cracks, rust spots and drilled holes on the
to be clean.
walls are maintained and repaired during shut-down.
Many cracks observed on the walls and floors were not
1.2.
smooth. Done
Defected doors are repaired and maintained to be in good condition.
1.3. Noted some rust spot on the floor of production area.
Most doors were not smooth, not close well, made of Change Control and Photo Attached
1.4. aluminum, with house knob (lever handle) and in poor
condition.
1.5. A lot of drill holes on the walls and doors of production area.
In most places walls edges which sharp, not smooth and
1.6.
difficult to clean.
All coarse covers will be replaced with smooth covers having even
The lamp plastic covers were coarse, splotchy with different
1.7. colors. July-2016
color.
Attached copy of Purchase Order No_____.
Tubular lamp open to environment is replaced with covers that is easy
to clean.
1.8. Using tubular lamp in many places which it difficult to clean.
If it is not done, please change the above statement to will be done
and give deadline.
Busted lamps are replaced with new one.
1.9. Some lamps were not working due to lack of maintenance. Done
Photo Attached.
Defected windows are repaired and maintained.
1.10. Some windows were in poor condition with tapes and silicon. Done
Photo Attached.
Failure to meet cGMP requirement for usage of non-
shedding wipes for cleaning as: The consumed underwear Gamma wipe (Non-fiber shedding cloth) dedicated for cleanroom is
male and female clothes were used to clean the machine in ordered.
2. Done
the clean production area under the recognition and Meanwhile, only approved cloth will be used for production areas.
realization of quality and production management that Attached copy of Purchase Order No_____.
shows the weakness of these departments. (Critical) (Clause:

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point 3.37, and annex 9 point 7 SFDA guideline)
Technical Manager will handle this position till suitable candidate is
hired.
Existence of key posts in the plant has not been occupied as
In job description of Production Manager and Technical Manager, it
3. the production manager. (Major) (Clause: point 2.3 SFDA Done
should highlight that Technical Manager will handle all daily affairs
guideline)
in absence of Production Manager.
Revised Job Description for Tech Manager is attached.
Failure to meet cGMP requirement for good documentation
constitutes while there is confusion in the documents Concerned staff retrained on Good Documentation Practice (GDP) to
distribution between the different departments of company handle the distribution between the different departments in the
4. Aug-2016
as HR department, QC labs, QA department, Engineering company.
department and Production. (Major) (Clause: principle of Attached copy of training record.
chapter 4 SFDA guideline)
The environment monitoring of class C area was not
5. accepted and have a (critical) findings as: (Clause: point 4.1, --- --
4.26, 6.9, annex 1 point 3 and 4 SFDA guideline)
Concerned staffs have been retrained.
5.1 Discrepancy between the raw data and mistake in the dates. Done
Training Record Attached.
Trend analysis for viable count is available for all production areas.
Attached Trend analysis for viable count.
Done
For non-viable, concerned staff trained to maintain the trend analysis.
5.2 No trend analysis for viable and non-viable data.
(Give timeline to complete as Will be done Soon terminology not
Timeline
accepted)
Training Record Attached.
In (SOP-02-M-004) environment monitoring program for
5.3
clean room many deficiencies as:
During the settle plate studies did dedicate the situation of Incorporated in SOP-02-M-004.
5.3.1 Done
production if it at rest or at operation. Attached SOP copy.
Incorporated in SOP-02-M-004.
5.3.2 Did not take the non-viable sample at rest situation. Done
Attached SOP copy.
Incorporated in SOP-02-M-004.
5.3.3 Did not dedicate the volume of air sample of non-viable test. Done
Attached SOP copy.
Did not dedicate the exactly time when it should do the Monitoring Frequency is determined by quality risk management.
5.3.4 Aug-2016
viable and non-viable test. The alert/action limits are dependent on the types of operations

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carried out.
The non-viable particles count (0.5 m) of 360 ampoules
5.4 filling room (class C) was not accepted for the following
reasons:
Environmental monitoring results are mainly required for class A & B
areas and this will be part of the batch release system, however, the
class C is monitored on weekly basis and some batches may not have
Most of non-viable results were exceed the required limit at the environmental monitoring details, we have started added the
03/11/2015, 09/11/2015, 16/11/2015, 19/11/2015 and environmental monitoring documents to the batch records since 2014
5.4.1 as per Egypt MOH recommendations during the last GMP Audit. PSI is
22/11/2015 etc. although the results also accepted by the
attaching the weekly environmental monitoring forms to cover the
quality department without justification. produced batches which have been prepared on this week because
we are not doing the environmental monitoring for each batch and
we are not doing it continuously. This is done as per the GMP for
cleanroom class C.
In 09/11/2015 environmental report some locations has not
considered in sampling due to constrain by production staff
the quality employee take non-viable samples from two
Concerned staff retrained to adhere Environmental Monitoring SOP.
5.4.2 location and leave the remaining three sampling points due Done
Training record attached.
the prohibition of the production staff. Although the batch
was released and accepted by the quality assurance without
justification
The Terminal sterilization process will be included in the process
validation and it will be done on line along with the process validation
and it will be part of the process validation protocol.
The terminal sterilization processes of some products were
not validated as Normal Saline glass 100 ml. In addition the Plan has been revised to finalize the process validation for the
remaining items in 2016 or whenever the manufacturing is performed
6. validity of the sterilization processes were not verified at Timeline
ahead of 2016.
scheduled intervals, at least annually. (Critical) (Clause: Copy of updated process validation list.
Annex 1 point 83 and 84 Annex 15 SFDA guideline) Copy of Process validation list for the remaining products.

The autoclave validation (every 6 months) will continue and it will be


done separately from the product sterilization method validation as

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per the related SOP.
The registered Technical Manager was not performing his
responsibilities and duty and did not have sufficient training
to meet required qualifications as stated in the SFDA Job Description has been revised for the Technical Manager and all
announcement number 29982 dated on 8/9/1436H about points relating to responsibility are included as stated in the SFDA
announcement number 29982 dated on 8/9/1436H.
7. duties and responsibilities of technical director, as the Done
Training conducted for Technical Manager
following were observed: (Critical) (Clause: chapter 1 quality Attached copy of approved Job Description
management and point 2.4 SFDA guideline and (Article 5 the Training record attached
Facilities and Pharmaceutical Law no. M/31 dated
01/06/1425H))
The technical manager lacked decisional power and was not
7.1 Incorporated in Job Description of Technical Manager.
fully independent from the acting manager.
Overlaps in responsibilities as QA, QC, Production etc.
Plant Organgram illustrates reporting system.
7.2 managers reporting to acting manager and technical Done
Attached Copy of Organogram
manager in parallel.
Vendors qualification, out sourcing activity and major
7.3 change control is not a part of technical manager Incorporated in Job Description of Technical Manager. Done
responsibilities.
All job description and responsibilities were not approved by Incorporated in Job Description of Technical Manager. Effective
7.4 Done
the technical manager and were not updated from 2012. immediate.
Not contribute of technical manager toward the recalling, Incorporated in Job Description of Technical Manager and Recalling
7.5 Done
compliance and corrective action. SOP has been revised.
New full covering shoes have been ordered to replace the plastic
The operators gown the plastic slippers shoes which already
slippers.
8. did not cover the foot. (Major) (Clause: point 2.15 and 2.18 May2016
Attached copy of Purchase order No____
SFDA guideline).
Attached Photos for the new proposed shoes.
The cleaning status of gowning room class C area was not Cleaning frequency has been increased to ensure the cleanliness.
SOP-03-047 (Clean room sanitization) has been revised and training
9. satisfactory as powder and dust noticed there. (Other)
done for concerned staff
(Clause: principle of chapter 3 SFDA guideline).
Training record attached
There was no maximum limit of differential pressure for all
10. production rooms (Other) (Clause: point 3.12 SFDA Study to set maximum limit of DP will be determined. Timeline
guideline).

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Weighing operators are not following gowning SOP of class C
Retraining done for concerned staff on SOP (name and no.)
11. area for instance non-sterile gloves were used. (Other) Done
Training record attached
(Clause: point 2.8 SFDA guideline).
Job work order raised and repair has been done for all leakages. SOP
Leakage observed from the chilled water circulation in many
(name and number) will be revised to handle such maintenance
places of preparation tank in class C area without
12. defects. Done
maintenance order. (Major) (Clause: point 3.34 SFDA
(we have to state in the maintenance SOP about rectifying the
guideline).
leakages)
Using a plastic water hose with rusty hose clamps to supply
WFI in class C room while the hose was not easy to clean and
Water hose has been replaced with pharmaceutical grade.
13. there is a risk of recession and contamination. (Major) Done
Photo attached.
(Clause: WHO quality assurance of pharmaceuticals water
for pharmaceutical use point 5.1 & 6.2)
The liquid hoses that were used in the manufacturing of we are working with a third party consultant to prepare a new
liquid products were neither dedicated nor covered in the cleaning validation protocols to repeat the cleaning validation for all
14. Timeline
cleaning validation. (Other) (Clause: point 3.37, 5.19-vii, lines as per the cleaning validation guidelines to cover the train of
Annex 15 point 36 and 38, Annex 20 point 2.4 SFDA). equipment which will include all product contact parts
Using a white Teflon in the pipe contact points in the
manufacturing of liquid products (preparation room). All gauges with Teflon pipe will be replaced of chilled water line with
15. Timeline
(Major) (Clause: point 3.1, 3.2, 3.9 and 3.10 SFDA diaphragm type.
guideline).
Using Red garden water valve (lever-type handle) and iron Red garden valves will be replaced with new valves from different
pipes to supply and transfer a water in class C area which supplier and these valves are made of stainless steel 316 L.
16. does not comply with GMP in class B. (Major) (Clause: WHO Attached copy of Photos for the new procured valves Timeline
quality assurance of pharmaceuticals water for Attached copy of Vendor certificate for the pipes
pharmaceutical use points 5.1 & 6.2). Attached copy of Vendor certificate for flexible pipes
Failure to meet cGMP requirement to good maintenance
17. practice for instance: (Major) (Clause: point 3.1, 3.2, 3.9 and
3.10 SFDA guideline).
Exposed electrical metal pipes are covered adequately. Concerned
17.1. Covering damaged electrical metal pipes by a tin paper which
engineering staff working in production has been trained. Done
reflects a poor maintenance.
Photo and training record attached.
17.2. Using rusty iron screws and tapes to seal the air suction ducts Concerned staffs trained on maintenance SOP.
Done
in class C area which reflects a poor maintenance. Training Attached.
17.3. There was a broken telephone in the corridor of class C Broken telephone instrument removed and replaced with good
Done
production area which reflects a poor maintenance. condition telephone instrument.

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Photo Attached.
Job work order raised to repair and maintain the defected
17.4. There was inoperative doors interlock system without any
interlocking doors. Done
maintenance or job orders.
Copy from job work order attached. Photo attached.
Using a scratchy plastic chair and drums and in poor All defected chairs and drums are replaced with good condition in the
18. condition inside the production class C rooms. (Other) Class C room. Done
(Clause: point 3.1 and 3.2 SFDA guideline). Photo Attached.
During the inspection and operation running, many
deficiencies were notices in the filling room 362 of grade C
19.
area as: (Major) (Clause: point 3.1, 3.2, 3.9, 3.10 and 3.32
SFDA guideline).
There were two paper-printing machines and office The printing machines are spare room area and will be used
19.1
whenever applicable. The computers have been removed from the Done
computer behind the filling machine.
filling rooms.
Plastic containers are replaced with good condition along with
There was dirty plastic container without identification label
19.2 identification label on them and concerned staff trained. Done
and with unknown use.
Photo Attached. Training record attached.
19.3 There was unclear rusty table and covered by foreign oils. Defected rusty table removed instantly from filling room 362. Done
Concerned staff training to store the cylinder in the dedicated storage
19.4 Store the cylinder of machine in the disinfectant trolley. area with proper condition. Done
Training record attached. Photo attached.
Room has been cleared from needless things and concerned staff has
19.5 Silicon oil and plastic sheets stored in the corner of the room. been trained. Done
Training record attached. Photo Attached.
Staffs working in the area have been retrained to prevent from
Store many spare parts inside the electrical panel cabinet of
19.6 storing such parts and to store in its dedicated area. Done
filling machine.
Training record attached.
Using electrical extension cord to provide the electricity with Electrical connections exposed to environment have been rectified to
19.7 Done
many exposed electrical wires. match with class C room requirements.
During the inspection and operation running, many
deficiencies were notices in the filling room 360. Of class C
20.
area as: (Major) (Clause: point 3.1, 3.2, 3.9, 3.10, 3.15, 3.32
and 5.18 SFDA guideline).
Store the spare parts inside the production room; however, The spare parts are stored in new dedicated store room and
20.1 Done
there is no spare part specific area for all production rooms. concerned staff has been trained.

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Photo attached of new spare parts room.
Training record attached.
20.2 Using rusty ladder inside the production room. Rusted ladder removed instantly. Done
The cooling unit of ampoule filling line have some
20.3
observations as:
20.3.1 Existence of rusty screws in the filling unit. Rusty screws have been replaced with new ones. Done
Job work order raised and repair has been done.
20.3.2 There was a leakage without maintenance Done
Copy of Job work order attached.
Rusty iron connected components and clamps will be replaced with
Using a rusty connected iron pipes and claims that are not in pharmaceutical grade. Meanwhile, rusted components will be
20.3.3 July-2016
pharmaceutical grade. treated well with passivasion to remove the rust.
Attached copy of Purchase Order No_____.
- Purchase order raised to fabricate capping machine with stainless
The capping machine of bottles in the filling room number Aug-2016
steel body.
305 was rusty and made of non-stainless steel which is not in
21. - Meanwhile, rust and stain has been treated, passivated and all
pharmaceutical grade. (Major) (Clause: point 3.34, 3.38 and Done
related parts are maintained in good condition.
3.39 SFDA guideline).
Attached copy of Purchase Order No_____.
During the inspection, many deficiencies were noted in the
autoclave receiving area and the following findings which are
22.
classified as (Major) were observed: (Clause: point 3.34, 3.38
3.39 and 5.13 SFDA guideline).
Autoclave trolleys are kept in dedicated area with status label affixed.
Storing the trolleys of autoclaving products in undedicated Concerned staff trained.
22.1 Done
area and without any cleaning status. Photo attached.
Training record attached.
The trolleys of autoclaving products were stained, scratched Trolleys cleaning SOP has been created, the cleaning and passivation
22.2 Done
with crooked and not in good condition. will be defined and done periodically.
All damaged trolleys / parts have been removed.
There are some phrases written on the trolleys as (not good)
Concerned operators working in the area has been trained to
22.3 which reflecting the lack of operators discipline in the Done
maintain discipline and GMP compliance in the area.
production area.
Training record attached.
Defected plastic pallets have been removed and replaced with a new
Using plastic pallets with scratching and not in good
22.4 plastic pallet. Concerned staff trained for cleanliness. Done
condition. In addition, pallets are not clean.
Training Record attached.
22.5 All rejection bags for the products during manufacturing All dust bins/rejected bins have been distinguished between Done

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were not identified. In addition, we found some ink and pharmaceutical waste and solid waste for its appropriate use.
disinfectant empty bottles with the rejected products. Concerned staff trained.
Photo attached.
Training record attached.
Ensure that you have SOP for waste management that handle
pharmaceutical waste and solid waste.
The inner surface and floor of autoclaves were rusty with
Autoclave management SOP has been revised to include passivation
22.6 stain and not in good state. (As autoclaves No. SBM01 and Done
process periodically to eliminate rust and stains.
SODI LAB).
Out of use capping machine has been removed from the production
Keep out of use control panel (CAP welding M/C) in the
22.7 area. Concerned staff trained to affix status. Done
receiving area of autoclave without status label.
Training record attached.
The door has been removed and the wall has been sealed/closed
There was undefined door that open directly to the external
22.8 permanently. Done
environment.
Ensure the door is not used as Emergency exit.
The floor near to the autoclaving area / receiving area has been
The trolleys railways on the floor of receiving area were replaced with stainless steel, the trolleys railway has been replaced
22.9 Done
difficult to clean and in poor condition. with a new one that easy to clean.
Photo attached.
The plastic partition wall between the autoclave receiving
Defected partition has been replaced.
area and secondary packaging area was broken with large
23. Photo attached. Done
holes and needs to be maintained. (Other) (Clause: point 3.2
SFDA guideline).
During the inspection, many deficiencies were noted in the
24. glass filling room as: (Major) (Clause: point 3.1, 3.2, 3.7, 3.10
and 3.34 SFDA guideline)
Concerned operator has been trained to use status label.
24.1 The filling room without status label. Done
Training record attached.
The glass filling door opens directly to gowning room which is class C,
then from this room the person is going to Class D area where the
person is crossing the bench and take the dedicated shoes and from
The door of filling room opens directly to the gowning room
24.2 that room the person open the door to unclassified area.
that is between the unclassified area and class C area.
I cant judge this unless I see the gowning area physically, as what the
inspector observed is in contradiction with PSI answer. But, if you are
sure, then dont change it.

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The glass-filling machine was rusty, stained with white silicon Rust and stain has been treated, passivated and all related parts are
24.3 Done
and needs to be maintained. maintained in good condition.
While the glass-filling machine was in clean status, we found The old caps have been removed, the operator and area supervisor
24.4 Done
some caps from the last batch. have been re trained for line clearance procedure.
The star wheel of the filling machine was outmoded with
24.5 New star wheel has been installed Done
many tapes and with shedding particles.
The broken measuring cylinder has been removed and replaced with a
24.6 Using a broken measuring cylinder for in process control. Done
new one.
The electrical wires and extensions have been removed and we have
kept the printer near to the electrical plug to avoid any electrical
Many exposed electrical wires and using electrical extension
wires exposed on that area.
24.7 cord to provide the electricity to the visual inspection Done
equipments and printer machine.
Visual inspection machine connection has been kept outside the filling
room.
Rust and oil present on the storage buffer tank has been cleaned. SOP
(Number and Name) have been revised to include physical check prior
There was a rust and strange oil on the storage buffer tank
24.8 to use and concerned staffs have been trained. Done
while it was in clean status.
Revised SOP attached.
Training record attached.
- Purchaser order for new pharmaceutical grade pipes will be
Aug-2016
The liquid pipes that used to transfer the product from buffer ordered.
24.9 tank to the filling machine were rusty, outmoded, non- - Meanwhile, the existing stainless steel pipe cleaned properly as the
Done
stainless steel and not in pharmaceutical grades. stainless steel pipes color has been changed from outside surface
not inside due to improper cleaning.
During the inspection, many deficiencies were noted in the
class D area and the following findings which are classified as
(Major) were observed: (Clause point 3.1, 3.2, 3.7 and 3.34
25. SFDA guideline & WHO quality assurance of pharmaceuticals
water for pharmaceutical use point 5.1 & 6.2 & Annex 5
point 4.2.8 WHO technical Report Series 961 and point 3.10
SFDA guideline.
Office diffusers will be replaced with swirl diffusers. Purchase order
25.1 Using of office air diffusers in most of production room. has been raised. Sept-2016
Attached copy of Purchase Order No_____.
25.2 Tubular lamp that are not easy to clean are used in class D The tubular lights will be changed to match the class D requirements. Timeline

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classified area and there in a risk recession
The production wall protection pipes were rusty and not in The rusty steel protection pipe will be changed and replaced with a
25.3 Timeline
pharmaceutical grade. new one to match the grade D requirements.
The disinfectant bottle has been labeled with proper label showing
the expiration date. Concerned staffs have been trained.
25.4 Using anonymous disinfectant with unknown expiration date. Done
Photo attached.
Training record attached.
Using a plastic water hose to supply the demineralized water
The improper water hoses have been removed from the area and
25.5 while the hose was not in good condition and there is a risk Done
replaced with a new one.
of recession and contamination.
Inappropriate procedures for handling and storage the
26. materials in production area, (Major) (Clause: point 3.8 SFDA
guideline), as the following had been observed:
Haemodialysis products for a while in the corridor to be transferred to
Finished Goods Store. Concerned staff trained to do not keep Finished
Goods in the corridor which must be transferred to FG store upon
completion.
Store finished Haemodialysis products and primary packaging Photo Attached
26.1 material for undefined time in the corridor of production Timeline
Training record attached.
area.
For primary packaging materials, all the pallets will be kept inside the
transit store only. Concerned staff trained.
Photo Attached
Training record attached.
We are monitoring the temperature of the transit store on daily basis,
Store the material in the transit storage area randomly for however, the temperature mapping study for transit store will be
26.2 unspecified time, while the area was not covered in the done, protocol is under preparation and will be executed soon. Timeline
temperature mapping study. Terminology of using Executed soon is not appropriate. Timeline
should be defined.
The operators poured WFI in undefined tank and keep it for Concerned staff trained to affix the status label of the bowl. Holding
undefined time (as stagnant water) then use it in the time study to store the WFI will be conducted. Meanwhile, WFI used
27. cleaning of classified area. (Major) (Clause: WHO quality for cleaning will be changed every shift. Timeline
assurance of pharmaceuticals water for pharmaceutical Timeline for WFI holding time study. Protocol to be prepared and
use points 5.1 & 6.2) executed.

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During the inspection, many deficiencies were noted in the
packaging area and the following findings which classified as
28.
(Major) were observed: (Clause: point 3.15, 3.34, 3.41, 3.44
& Annex 1 point 124 SFDA guideline)
28.1 The red ink of stamp was stained and distributed on the
packaging line.
The vials visual inspection operators did not take breaks
28.2
sometimes while the procedure gives them break each hour.
28.3 The rejected vial container was not identified.
The irrigation packaging line was out of use without status
28.4
label.
The Atropine inspection line was not separated for the
28.5
packaging line of plastic ampoules.
The packaging line of plastic ampoule have some deficiencies
28.6
as :
Did not challenge some automated sensors as the online
28.6.1
balance and sensor of label.
28.6.2 Did not calculate the rejected products and just damage it.
The chair of operator tied to the packaging machine by rusty
28.6.3
iron chain.
Some parts of packaging line were damaged and fixed by
28.6.4
plastic tapes.
SOP (Number and Name) has been revised to increase the frequency
The pre-filter of air laminar flow (90-1000ml) receiving area
of checking pre-filter status and cleaning.
29. have color sports without justification. (Other) (Clause: Done
Concerned Staff trained.
principle of chapter 3 SFDA guideline).
Training record attached.
IQ OQ documents for BMS is available and it is approved and done
There was no qualification for the building management successfully, however, the PQ part is going on, the protocol is under
30. electronic system of the new production area. (Major) preparation and PQ test will be done immediately.
(Clause: Annex 15 point 1 SFDA guideline). Meanwhile, all related parameters are recorded manually.
Copy of approved IQ and OQ protocols and reports attached.
Deficiencies were noted which related to the organogram
31. procedure (SOP-13-005) as: (Major) (Clause: point 4.2, 4.3
and 4.5 SFDA guideline).
31.1. The organogram was not updated from 2014 while the SOP SOP has been revised and organogram updated. Done

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state it should be updated yearly.
The SOP (organogram procedure) has not been training by
31.2. Concerned staff trained. Done
related staff.
New organogram approved by the Technical Manager.
31.3. In addition, the last organogram was not approved. Copy of training record attached. Done
Copy of approved Organogram attached
Deficiencies were noted which related to the drawings
management system and maintenance utilities department
32. (SOP-04-048) as: (Major) (Clause: point 4.2, 4.3 and 4.5
SFDA guideline & point 5.4.1 WHO quality assurance of
pharmaceuticals water for pharmaceutical use)
The new layouts have been prepared for all PSI premises and have
been approved by QA Manager and Authorized by Factory Technical
32.1 There were mistakes in the layouts of production area Done
Manager.
Attached copy of new lay out
SOP created under QA department to control layouts. Master layouts
32.2 There was no master copy for all layouts. will be kept in QA department only.
Attached copy of new SOP.
Under QA control, and controlled copies (with controlled stamp) will
The layout copies were not controlled and without stamp as
32.3 be distributed through distribution document to the concerned
SOP recommended.
department.
The layouts copies were not kept in safe and key condition as Concerned staff trained.
32.4 Done
SOP recommended. Attached copy of training record.
The SOP did not include the reviewing date to layouts and all The effective date and reviewing date has been considered in the new
32.5
manufacturing layouts were not approved and updated. layout management SOP.
There are many products have been validated since 2013 up to date,
there are some slow moving products (No Market demand) which
Most of products without process validation and some of
have been not done yet, however, Plan has been revised to finalize
them produced continuously and this point from the last
33. the process validation for the remaining items in 2016 or whenever Timeline
inspection 2014 and still unresolved. (Major) (Clause: Annex
the manufacturing is performed ahead of 2016.
15 SFDA guideline).
Copy of updated process validation list.
Copy of Process validation list for the remaining products.
The rejection products were not considered in the calculation
The rejected product is being calculation and it is part of
of reconciliation percentage, and for more all batches within
34. reconciliation process which is recorded in the batch record. Done
reconciliation percentage and pass. (Major) (Clause: point
All bottles are calculated after sterilization phase because the number
4.18, 5.8 and 5.56 SFDA guideline)

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of bottles is identified and known, the labelled and packed bottles are
calculated as well, so the number of rejected bottles is calculated
precisely without any mistake.
There are some cases when the rejected bottles are thrown to the
dust bin without physical counting and checking by production and
QA department.
Concerned staff trained.
Training record attached.
Recovery time SOP is prepared, the recovery time study for all clean
rooms will be done, five areas have been completed (New bags filling
There was no procedure to calculate the recovery time when area & Ampoule filling BP 362 Glass filling irrigation filling
the production shall start after the electrical shutdown in the BP324), the recovery time for other areas are in progress and planned
35. Done
production area. (Major) (Clause: point 4.1 and 5.4 SFDA to complete in May 2016.
guideline). Attached copy of Recovery time SOP.
Attached copy of Recovery time test for bags area Ampoule area
BP 362 Glass filling area (Groninger) Irrigation Filling area BP324.
The responsibility of clean rooms fumigation was assigned to one
technician and there was no accountability for the whole process.
We have decided to make fumigation SOP for each production area as
per the followings:

Fumigation SOP for 1st Floor (Solution Preparation Unit


Bottle Pack Machines).
Fumigation SOP for second floor (Groninger Glass filling
The fumigation process implementation and (SOP-03-068) Irrigation Filling).
36. procedure have (Critical) deficiencies as: (Clause: Annex 1 Fumigation SOP for 3rd Floor (Bags Filling)
point 61 and 63 SFDA guideline).
Each SOP has stated the following procedure:
Area volume and solution volume have been considered as
per the supplier recommendations
The necessary precautions that need to be considered during
the fumigation.
Responsibility which has to be the qualified, trained &
experienced operator.
Accountability which has to be the production manager for

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that area.
QA monitoring for the fumigation process.
Fumigation contact time and the recovery period as per the
supplier.
In addition to that, the supplier has been contacted and he has
provided all related documents to this subject which includes
(effectiveness study Certificates like SFDA Medical device / CE Mark
Safety recovery time details - contact time details MSDS), these
documents have been collected to justify the old procedure.

However, we are in process of ordering a new instrument for


measuring the hydrogen peroxide during the fumigation process and
measurement will be done during the contact time and the recovery
time.

This instrument will be used to cross check and validate the accuracy
of the recommended contact time and the recommended recovery
time by supplier.

The Purchase request has been approved and the instrument will
reach after one month.

In addition to that, we are going to make the effectiveness study for


the fumigation process, the protocol is under preparation and will be
finalized soon.
Environmental monitoring study will be done to check the
effectiveness of the fumigation process and we will collect the viable
count reading and we will monitor the result carefully that we can
decide the frequency for fumigation.
Attached copy of Purchase Order No_____.
Point 8.2.3. Ask to close all drains by aluminum foil during
36.1
the fumigation while they did not practice it.
Using 1000 ml of fumigation substance for each room while
the supplier recommends using 500 ml for each 500 m3
36.2
without justification or computation to the volume of the
production rooms.

Page 14 of 23
Sometime they do the fumigation while the HVAC running as
36.3
the employees stated.
Always they fumigate one product room while the rest
36.4
production rooms running.
The recovery time after fumigation was one hour without
36.5
supporting data or justification.
The fumigation repeated every two months without
36.6
justification.
The fumigation process implementation in the micro clean
test room and (SOP-02-M-032) procedure have (Major)
37.
deficiencies as: (Clause: Annex 1 point 61 and 63 SFDA
guideline).
Did not dedicate the quantity of fumigation substance Area volume and solution volume have been considered as per the
37.1
(Hydrogen Peroxide). supplier recommendations
Recovery time has been changed to match the supplier
The recovery time after fumigation was three hours without
37.2 recommendations, which is 1 hour. Traceability test should be
supporting data or justification.
conducted and validated for 1 hour as recovery time.
The fumigation is repeated on weekly basis as per the existing SOP.

In addition to that, the supplier has been contacted and he has


provided all related documents to this subject, which includes
(effectiveness study Certificates like SFDA Medical device / CE Mark
Safety recovery time details - contact time details MSDS), these
documents have been collected to justify the procedure.

However, we are in process of ordering a new instrument for


The fumigation repeated every two months without
37.3 measuring the hydrogen peroxide during the fumigation process and
justification.
measurement will be done during the contact time and the recovery
time.

This instrument will be used to cross check and validate the accuracy
of the recommended contact time and the recommended recovery
time by supplier.

The Purchase request has been approved and the instrument will
reach after one month.

Page 15 of 23
In addition to that, we are going to make the effectiveness study for
the fumigation process, the protocol is under preparation and will be
finalized soon.
Environmental monitoring study will be done to check the
effectiveness of the fumigation process and we will collect the viable
count reading and we will monitor the result carefully that we can
decide the frequency for fumigation.
Fumigation with hydrogen peroxide was performed periodically
every two months as a part of area sanitization.
Attached copy of Purchase Order No_____.
The equipment cleaning procedure (SOP-03-048) has (Major)
38.
deficiencies as: (Clause: point 3.37 SFDA guideline)
They dipped a piece of wipe in the disinfectant solution The related SOP (SOP 03 048) has been revised to include these
38.1 repeatedly during the cleaning of equipment observations. Done
Copy of SOP attached.
Did not dedicate the type of cleaning wipes that they should The related SOP (SOP 03 048) has been revised to include these
38.2 use in cleaning. observations. Done
Copy of SOP attached.
The monitoring of HEPA filters differential pressure is done every 3
months and there is a daily checklist which is implemented on all
clean rooms, the checklist include monitoring of Air Temperature
The monitoring of HEPA filters differential pressure done (supply & return) Bag filter differential pressure Duct filter
every three months while there was no procedure to deal differential pressure visual inspection for Fan & coil section.
39. with it if some things happened within three months. (Major) Done
(Clause: Annex 5 point 8.2.13 and 8.2.14 WHO Technical The daily monitoring is done continuously and any abnormality during
Report Series 961). the daily monitoring will be reported and will be corrected as per SOP
(Name and Number).

Copy of Daily checklist for air handling units (Form No: FM 04 032)
In the validation of 5% Dextrose Normal Saline terminal
40. sterilization validation method some (Major) deficiencies as:
(Clause: HTM 2010 guideline).
In a sterilization phase, the temperature should be more The sterilization method validation for this product product was done
40.1 Done
than 121C for 20 minute, while it was from 120.86C to in 2010, during that period the SOP stated that the sterilization cycle

Page 16 of 23
120.92C. acceptance limit is 121 C 1C and F08 was one of the releasing
criteria (if F08 is more 30 for 12 minutes), however, the SOP is revised
in 2014 and the limit has been changed to become 121C + 2C and
anything below 121 is not accepted and we are following that system
since 2014.
The acceptance criteria for sterilization method validation is based on
the sterilization phase (Time Pressure Temperature), there is no
Did not consider the cooling phase in the sterilization
40.2 certain acceptance criteria / limit for cooling phase, however, our Timeline
method validation.
data loggers are recording the data from heating phase till cooling
phase and we can include the cooling phase in the sterilization cycle.
The accuracy of temperature data loggers in the validation of The accuracy of temperature data loggers in the validation of
40.3
sterilization method was 2C. sterilization method was 1C.
The biological indicators were not used in the old sterilization method
The biological indicators were not used in the sterilization validation, however, the new SOP stated that the sterilization method
40.4 Timeline
method. validation shall be done by using bio indicator and it was started since
end of 2014.
Only one sterilization cycle done in the sterilization method validation
at the time and the list of sterilization method validation showing the
Only one sterilization cycle done in the sterilization method
40.5 number of cycles that have been done for each and every products, Timeline
validation.
however, this sterilization method validation will be part of the
process validation and will be implemented soon.
We are working with external consultant to prepare a new cleaning
The cleaning in place (CIP) methods of Groninger line 1 & 2
validation protocol to repeat the cleaning validation for all lines.
41. filling machine and transferring hoses were not validated. Timeline
Copy of Cleaning validation contract with external consultant is
(Major) (Clause: Annex 15 SFDA guideline).
attached.
Cleaning validation has been completed for several lines and was
approved and documented like Metronidazole Fluconazole 15 %
KCL Ciprofloxacine Magnesium Sulphate and Lidocaine , all these
items have been considered as the worst case scenario and the
All nine product storage tanks and Bram bag filling machine cleaning validation has been decided to become 3 cycles of CIP and
42. without cleaning validation. (Major) (Clause: Annex 15 then SIP cycle to get the effective cleaning results. Timeline
SFDA guideline).
Also we have arranged in house training program for technical team
on cleaning validation subject by third party consultant to increase
the awareness of the cleaning validation subject.

Page 17 of 23
In addition to that, we are working with external consultant to
prepare a new cleaning validation protocol to repeat the cleaning
validation for all lines.

Attached copy of Cleaning validation protocols.


Attached copy of Cleaning validation training documents and related
forms
Attached copy of Cleaning validation contract with external
consultant.
The tank has been removed from the area and will not be used
anymore inside the Solution Preparation Unit.

The mobile transferring tank sterilization in place (SIP) and


We are working with external consultant to prepare a new cleaning
43. cleaning in place (CIP) were not validated. (Major) (Clause: Timeline
Annex 1 point 27 SFDA guideline). validation protocol to repeat the cleaning validation for all lines.

Attached copy of Cleaning validation contract with external


consultant.
The PQR of 5 % Dextrose in Normal Saline 500 ml NPVC Bags was not
done till the time of audit. However, all raw data were available for all
the products.
Products annual reviews for 2015 were not ready until the
44. date of inspection visit without justification. (Major) (Clause: Timeline
We have started the compiling the PQR and we have completed
point 1.4 SFDA guideline).
around 50 different products.

The other PQRs are going on and will be finalized soon. Timeline
The sterilization in place (SIP) of the liquid filling line filters
45. have (Major) deficiencies as: (Major) (Clause: Annex 1 point
27 SFDA guideline).
135C is the maximum temperature recommended by the supplier for
135C is the temperature recommended by the supplier for sterilization, we are sterilizing the filter at 121C 130 C which is
45.1 sterilization while the SIP at 121C to 130C without within the supplier recommendations, SIP validation is done during
validation studies. process validation and during the machine qualification and found
satisfactory.
In addition, some filters SIP at 120C for 30 minutes as 0.9% The SIP cycle is done at 121 C and the recommended time is 20 45
45.2
w/v NaCl IV infusion. While there procedure required 45 Minutes as per the batch record, there are some filling machines

Page 18 of 23
minutes at 121C to 130C. (BP362) is considering the F08 automatically and the sterilization time
may vary depending on the pressure, this system is (built in) and the
machine qualification was done successfully. While for other
machines which are not considering the F08, we are using SIP cycle at
121 C for 30 minutes which includes (Ampoules filling machines
BP324 BP360 BP305)
The supplier has recommended a differential pressure to be NMT 1.0
The SIP of filter with pressure range 1.4 Bar while the
bar, which means the difference between the steam line pressure and
45.3 supplier recommendation pressure range is not more than
the machine pressure should be NMT 1.0 bar which is matching the
1.28 Bar.
existing procedure.
The number of filter sterilization was not considered while
We have revised the SOP to include the number of sterilization for
45.4 each supplier recommended a specific number of
each filter as per the supplier recommendations.
sterilization.
The SOP has been revised to include the details about the filter types
The filter management procedure (SOP-03-054) did not and approved suppliers
45.5
contain the details of filters types and suppliers. Attached copy of Filter suppliers documents
Attached copy of Filter management SOP
Our reference for conducting on-going stability study for registered
well established products is the GCC guidelines for stability testing
version 3.2 , date of implementation 03/05/2011 which is also the
reference submitted and published at SFDA web site guidelines
since 26/05/2013
In this GCC guideline , point # 3.2.12 (on-going stability studies ) , page
# 34 , it is clearly mentioned that , for conducting on-going stability
at least one batch per year of product manufactured in every strength
Failure to meet cGMP requirement regarding number of
and every primary packaging type should be included in the stability
46. batches used in ongoing stability studies, which do not allow
program (unless none batches is produced during that year ) . PSI
trend analysis. (Major) (Clause: point 6.29 SDFA guideline).
follows this point exactly by issuing the SOP (SOP-14-009) for on-going
stability study activities and had been implemented since 11/11/2014
.
When the same GCC guideline insist to study more than one batch in
stability study , it is clearly mentioned in point 3.2.2 page # 21 (
selection of batches ) for routine stability study Data from stability
studies should be provided on at least three primary batches of the
FPP . this means the GCC & all international guidelines is more specific

Page 19 of 23
and clear for the number of batches required for conducting both
routine stability study and on-going stability study.
For trend analysis ; the same GCC guideline mention in same point
3.2.12 and page 34 the number of batches and frequency of testing
should provide sufficient data to allow for trend analysis BUT it is not
clearly mention that these number of batches are required per each
year and so as per our SOP , we collect one batch from each product
in each strength and each packaging material per each year and
conduct trend analysis for this particular batch along its shelf life and
then the next year we collect the same product and same strength
and same packaging material and apply for trend analysis also and
continuously every year we shall do the same (cumulative batches
after some time and give the sufficient data of trend analysis) .
In addition to that theory, we are following the written commitment
required by SFDA during registration of any product to conduct on-
going stability study at least one batch per year (section 3.2.P.8.2).

Copy of below attached:


- GCC guidelines for stability testing version 3.1 , chapter 3.2.12 ongoing
stability study page 34 of 47.
- GCC guidelines for stability testing version 3.1 , chapter 3.2.2 ongoing
stability study page 21 of 47
- On-Going stability study SOP (PSI internal SOP-14-009)
- Proposals for trend analysis conducted over random selected five running
products for batches collected on three different years
- Inquiry letter received from SFDA during registration of new products and
mentioned clearly at one point # 13.A that a commitment to conduct on-
going stability studies at least one batch per year as per section 3.2.P.8.2 is
required and so , there is no any contradiction or conflict between this
inquiry and the GCC guidelines as well .
The issue has been reported to QA and deviation was initiated by
In the deviation report number UD/PRD/003/16 the steam
production department. The product has been checked physically and
valves disrupted and some sticky ampoules of Lidocaine 1%,
found some ampoule are sticking to each others slightly.
Batch number 119904-A3 were noted and affected, while the
47. The autoclave was kept On Hold, job order has been initiated to
company remove sticky ampoules and check some quantity
maintenance, the steam valve has been replaced, empty cycle was
of batch then release the batch without any risk tolerance.
performed and then autoclave revalidation was done then the
(Critical) (Clause: points 5.15 and 5.39 SFDA guideline).
autoclave was released to production again.

Page 20 of 23
The first layers of each trolley have been destructed and as an extra
precautions, the second layer of each trolley was rejected too.
The packing line is having a pressure test for all ampoule, the pressure
limit is between 1.8 2.1 bar to detect any leakage that could
happen, the ampoules are kept under the pressing belt for 10 seconds
and inspectors are checking the ampoules against any defect which
includes the leakage
The product (1 % lidocaine) is filled in plastic ampoule and sterilized at
106 C and the same product is filled in glass bottles and sterilized at
121 C which means the product is not affected with high temperature
(107.2 C).
As a preventive action for releasing products without proper
investigation and complete risk assessment, a new Detailed Risk
Assessment SOP is under preparation and will be used for any
deviation whenever applicable, the risk identification Risk control
and risk mitigation will be included in details.

Copy attached for below:


Deviation report.
CAPA report.
Job order for autoclave repairing.
Empty cycle.
Autoclave revalidation cycle.
48. Found Blank Found Blank
In batch manufacturing record (BMR) batch number 119291,
49. some deficiencies have been noted as: (Major) (Clause:
points 2.5 & chapter 4 SFDA guidelines).
The monitoring and inspection of packing line should be
done each one hour while the operators do the test every Concerned staff retrained.
49.1 Done
two, three, or four hours without justification and under Copy of training record attached.
quality assurance vision.
The in-process control quality assurance volume and in-
process check report should be done each 90 minute while Concerned staff retrained.
49.2 Done
the operators do the test every two hours or more without Copy of training record attached.
justification and under quality assurance vision.
49.3 Miss of some signatures in the batch record as: Concerned staff retrained. Done

Page 21 of 23
Copy of training record attached.
49.3.1 In microbiology laboratory environmental monitoring report.
In physical check report at start of filling-ampoule machine
49.3.2
that used to measure the weight of ampoule.
The insecticides in the warehouse have been repaired.
Several insecticides in the raw and packing materials
The ENMA utilities have been instructed to check the insecticides for
50. warehouse were not working, e.g. (No. STR8-TSK-009)
all factory premises on weekly basis as per SOP.
(Other) (Clause: point 3.4 and 4.26 SFDA guideline).
Photo of the warehouse insecticide.
The receiving area in the raw and packaging materials
The receiving area has been identified with proper label.
51. warehouse was not identified. (Other) (Clause: point 3.2 and Done
Photo of the receiving area attached.
3.20 SFDA guideline).
The sampling room and procedure have (Major) deficiencies
52.
as: (Clause: point 4.22 and 6.11 SFDA guideline).
52.1 There was no list of light sensitive materials. List of sensitive product has been prepared and added to the SOP. Done
There was some discoloration (corrosion) in some stainless
All the old rusty wheels of the SS sampling table have been changed
52.2 steel pallets that used to sampling and in the laminar air Done
with new wheels, LAF panel cleaned to remove the rusty appearance.
booth.
There was some maintenance tools, gowning and unstated
52.3 All these items have been removed the cabinet. Done
sampling tools inside the sampling tools dedicated cabinet.
Missing to record same cleaning process in the cleaning The QC technicians have been retrained on Good documentation
52.4 Done
logbook. practice SOP to fill the complete details in the logbook.
52.5 The sampling booth without qualification status label. The qualification tag has been added. Done
The changing of wooden pallet step has been added to the SOP.
Based on SOP-02-F-016, did not mention the changing of
52.6 Attached copy of revised SOP (SOP 02 F 016). Done
wooden pallet to stainless steel pallet.
Attached Copy of Training record for QC technicians
Job order has been initiated for this incident on 29 / 02 / 2016 and
The temperature of finish products warehouse exceed the
was forwarded to maintenance department for corrective action, the
53. limit (25.9 C) in sensor C7 and the alarm was not worked. Done
action has been taken.
(Other) (Clause: point 3.19 SFDA guideline)
Attached copy of Copy of the job order
There was no training record for Irshad Ahmed to Sap
54. system, while he have user access to SAP system. (Other) SAP Training document for Mr. Irshad is attached. Done
(Clause: Annex 11 point 1 SFDA guideline)
The reference samples are located inside the FG store area under the
Store reference samples in the rejected materials dedicated
55. lock and key (QA control), the area is having a dedicated place for Done
area. (Other) (Clause: point 3.18 and 3.23 SFDA guideline)
reference samples and on the other side, there are several locations

Page 22 of 23
for complained / recalled items Market returned goods Expired
items rejected items.

The area has been checked again and rearranged again in proper way
to avoid any confusion
The humidity is monitored inside the finished goods by using form No:
The humidity was not monitoring in the finishing product FM 06 016 Rev. 02.
56. Done
warehouse. (Other) (Clause: point 3.19 SFDA guideline) Attached copy of Temperature and relative humidity monitoring
sheet.
Appropriate storage space shall be provided for the storage of the
Store some products samples outside the dedicated cabinet products under testing.
57. directly on the floor. (Other) (Clause: point 3.27 SFDA An additional cupboard to be dedicated for the storage of the Done
guideline) products under testing.
Attached Photo for the additional cupboard.
The cleaning report form FM-02-M-207 has been modified to include
only the cleaning of Microbiology Laboratory. Also, a separate SOP
The cleaning procedure of micro lab (SOP-02-M-015) have
(SOP 02 M 043) has been prepared for the cleaning of
some deficiencies as; (Major) (Clause: point 3.2, 4.2, and 4.3
equipment of Microbiology Laboratory. Both SOPs and related data
58. SFDA guideline) Done
recording forms / log book are ready.
Concerned staff trained.
Where are the deficiencies?
Attached copy of Cleaning SOP of Microbiology lab equipment.
Attached copy of training record.
TOC is monitored through daily sampling procedure and there is no
continuous monitoring for TOC.
There was no continuous measurement for TOC (total
59. organic carbon) of loops 1, 2, and 3. (Major) (Clause: point We have prepared a change control for continuous TOC monitoring Done
7.3 chapter 1, water for pharmaceutical use, WHO guideline). for Loop 1, 2 and 3, also we have received offers for TOC monitoring
system for water treatment unit and it will be procured after having
the complete technical details.

Page 23 of 23