Page 1/23

Les Laboratoires SERVIER Industrie

905, route de Saran - 45520 Gidy - France








Audit Report:



C
C
I
I
F
F
A
A
R
R
M
M
A
A
-
-
P
P
E
E
R
R
U
U


( (3 30 0
T TH H
A AN ND D 3 31 1
S ST T
O OF F J JA AN NU UA AR RY Y 2 20 01 12 2) )








Date : 20/03/2012 From : Benot SCHNEE

To : Antonio CASTILLO
Roberto CORTEZ
Claudia KUBOKAWA
Patricia SALAS
Ruben Dario VILLENA LEON

Copies : Jean Louis DAUDET
Philippe DARTIGUELONGUE
Philippe GAUCHER
Pierre FARALDO
Cline GAUTRAND-POIREE




Page 2/23
CONTENT
I I. . I IN NT TR RO OD DU UC CT TI IO ON N . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 3 32 2
1 1. .1 1 O OB BJ JE EC CT TI IV VE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 3 32 2
1 1. .2 2 P PE EO OP PL LE E M ME ET T . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 3 32 2
1 1. .3 3 P PR RE ES SE EN NT TA AT TI IO ON N O OF F C CI IF FA AR RM MA A . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 3 32 2
1 1. .4 4 S SE ER RV VI IE ER R P PR RO OD DU UC CT TS S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 3 32 2
I II I. . F FA AC CI IL LI IT TI IE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 4 42 2
2 2. .1 1 W WA AR RE EH HO OU US SE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 4 42 2
2 2. .1 1. .1 1 O OR RG GA AN NI IS SA AT TI IO ON N : : . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 4 42 2
2 2. .1 1. .2 2 P PR RO OC CE ES SS S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 4 42 2
2 2. .2 2 S SA AM MP PL LI IN NG G A AR RE EA A . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5 52 2
2 2. .3 3 M MA AN NU UF FA AC CT TU UR RI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5 52 2
2 2. .3 3. .1 1 C CL LO OA AK KR RO OO OM MS S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5 52 2
2 2. .3 3. .1 1 W WE EI IG GH HI IN NG G A AR RE EA A . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5 52 2
2 2. .3 3. .2 2 W WA AS SH HI IN NG G A AR RE EA A . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5 52 2
2 2. .3 3. .3 3 G GR RA AN NU UL LA AT TI IO ON N . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 6 62 2
2 2. .3 3. .4 4 C CO OM MP PR RE ES SS SI IO ON N . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 6 62 2
2 2. .3 3. .5 5 I IN N P PR RO OC CE ES SS S S ST TO OR RA AG GE E A AR RE EA AS S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 6 62 2
2 2. .3 3. .6 6 C CO OA AT TI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 6 62 2
2 2. .4 4 P PA AC CK KA AG GI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 7 72 2
2 2. .4 4. .1 1 P PR RI IM MA AR RY Y P PA AC CK KA AG GI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 7 72 2
2 2. .4 4. .2 2 S SE EC CO ON ND DA AR RY Y P PA AC CK KA AG GI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 8 82 2
2 2. .5 5 L LA AB BO OR RA AT TO OR RY Y . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 8 82 2
2 2. .5 5. .1 1 P PH HY YS SI IC CO O- -C CH HE EM MI IC CA AL L L LA AB BO OR RA AT TO OR RY Y . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 8 82 2
2 2. .5 5. .2 2 S ST TA AB BI IL LI IT TY Y S ST TU UD DI IE ES S A AR RE EA A . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 9 92 2
2 2. .6 6 U UT TI IL LI IT TI IE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 9 92 2
2 2. .6 6. .1 1 H HV VA AC C S SY YS ST TE EM M . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 9 92 2
2 2. .6 6. .2 2 P PU UR RI IF FI IE ED D W WA AT TE ER R S SY YS ST TE EM M . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 9 92 2
I II II I. . Q QU UA AL LI IT TY Y R RE EV VI IE EW W. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 10 02 2
3 3. .1 1 M MA AN NU UF FA AC CT TU UR RI IN NG G A AN ND D A AN NA AL LY YT TI IC CA AL L F FI IL LE ES S R RE EV VI IE EW W . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 10 02 2
3 3. .1 1. .1 1 B BM MR R/ /B BP PR R . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 10 02 2
3 3. .1 1. .2 2 A AN NA AL LY YT TI IC CA AL L F FI IL LE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .1 1. .3 3 S ST TA AB BI IL LI IT TY Y S ST TU UD DI IE ES S . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .1 1. .4 4 P PR RO OD DU UC CT T S SH HE EE ET T . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .1 1. .5 5 A AN NN NU UA AL L S SA AM MP PL LI IN NG G . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .2 2 Q QU UA AL LI IT TY Y S SY YS ST TE EM M . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .2 2. .1 1 S SE EE E A AN NN NE EX X . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 11 12 2
3 3. .3 3 C CO ON NT TR RA AC CT T . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 12 22 2
3 3. .4 4 G GM MP P C CE ER RT TI IF FI IC CA AT T . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 12 22 2
I IV V. . C CO ON NC CL LU US SI IO ON N . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 1 12 22 2
ANNEX 1: QUALITY CHECKING............................................................................................ 132
ANNEX 2: ACTION PLAN ................................................................................................... 162
ANNEX 3: PRODUCT SHEET ............................................................................................... 192
ANNEX 4: GMP CERTIFICATE .............................................................................................. 232

Page 3/23

I I. . I IN NT TR RO OD DU UC CT TI IO ON N
1 1. .1 1 OBJECTIVES
In the context of our partner follow-up, the IDPT proceeded to a quality and technical audit
of the licensee GRUNENTHAL and its partner CIFARMA.

The items assessed during the audit were:
Pharmaceutical building review (Warehouse, Packaging, Laboratories, Utilities)
Products & Quality System review (SOP, etc.)

The audit of CIFARMA has been performed in collaboration with the GRUNENTHAL qualified
Person; M. Roberto CORTEZ.
1 1. .2 2 PEOPLE MET
During this audit, the CIFARMA persons met are:
.. Technical Director Patricia SALAS
.. Process Managing Antonio CASTILLO
.. Quality Assurance Manager Claudia KUBOKAWA
.. Quality Control Manager Ruben Dario VILLENA LEON
1 1. .3 3 PRESENTATION OF CIFARMA
Official name: CIFARMA
Address Carretera Central Km 3.0 N1315 Santa Anita, Lima, Peru
Pharma forms: Solid (tablet, Capsule), Liquid (Syrup), Pasty product (cream, ointment),
suppository
Cosmetic products
Production for other international companies: GRUNENTHAL, VIFOR, SANOFI, NOVARTIS,
BOEHRINGER INGELHEIM
Volume (total): 350 million tablets per year (SERVIER Products represent around 6%
with 21 million tablets per year)
Plant area: 3300 m
ISO Certifications: 9001/14001/18001
Pharma Certifications:
Peru (DIGEMID): GMP & BPL
Columbia (INVIMA): GMP
Personal: Processing 23 people / Packaging operation 47 people
CIFARMA work for the SERVIER license owners for 14 years
1 1. .4 4 SERVIER PRODUCTS
PRODUCT NAME PRESENTATION SHELF LIFE CIFARMA OPERATIONS
Arcalion Blister Alu/PVC Full Manufacturing
Daflon 500 mg Blister Alu/PVC 1st and 2ndary Packaging
Diamicron MR 30 Blister Alu/PVC 1st and 2ndary Packaging
Natrilix SR 1.5 mg Blister Alu/PVC 1st and 2ndary Packaging
Vastarel MR 35 Blister Alu/PVC 1st and 2ndary Packaging

Page 4/23
I II I. . F FA AC CI IL LI IT TI IE ES S
2 2. .1 1 WAREHOUSES
2 2. .1 1. .1 1 O Or rg ga an ni is sa at ti io on n: :
The warehouses are physically divided into different areas:
Raw material
Packaging item
Closed area dedicated to the imported bulk product
Dedicated area for product temperature sensitive

The area dedicated to the Products to be destroyed is located outside the main warehouse.

The warehouse counts around 26 racks lines of 4 levels (1000 pallets positions).
2 2. .1 1. .2 2 P Pr ro oc ce es ss s
At reception, materials are cleaned, weighted, registered into the ERP system (SAP) in
quarantine status and sampled by the QC dept.
Then, materials are transferred to the dedicated warehouses (Raw Material, Bulk, Packaging
material articles, temperature sensitive products area) to the relevant location (given by the
ERP system).

The good practices are followed and clearly documented:
Access restricted to the authorised personal only
ERP system that ensure the materials traceability and status
Status identification (quarantine, sampled, released) under QC responsibility
Temperature and humidity registered twice a day (Temp [10; 30]C RH% <70%)
Pest system in place in most of the warehouses
FIFO (First In First Out) policy guaranteed by the ERP system

It is important to underline that CIFARMA does not have a finish product warehouse since
CIFARMA is working only under order and send directly the finished product to its customers
warehouse.

Nevertheless some points have to be improved (cf. below).

Points to be improved:
The manufacturing area is protected by a pest control program but not the warehouse
(absence of insectocutor and pest system) - Traps and insectocutors to be added to ensure
the warehouses protection.
We recommend CIFARMA to close the warehouse door to avoid any temperature increase
of the warehouse and to protect the warehouse against the pests.
CIFARMA has to pay a particular attention to the storage conditions of the imported bulk
products and avoid letting the product waiting for outside (only protected by a canopy).
The waiting area (for the finished product) is quite small, in case of an important order
(quantity) the space dedicated is not sufficient.
Weighing system: The scale calibration has to be revised; indeed the scale range is 10 kg
to 750 kg when the calibration program is done with a 500 kg mass only.

Page 5/23
2 2. .2 2 SAMPLING AREA
The sampling area, well designed (Material and personal Airlocks) and equipped (Laminar
flow), is located into the reception warehouse.

The good practices are followed:
API: 100 % of the containers are sampled for identification
Chemical and physical analysis for the complete sample
Excipient: Sampling of 1 + N containers
2 2. .3 3 MANUFACTURING
The design of the manufacturing plant and the internal fittings used for the clean areas are
generally satisfactory (minimum ISO 8 classified, airlocks for each rooms, corridor separation
between the different pharmaceutical forms working area, resin floor, clean partition
panels).
Note: Due to the presence of product inside the manufacturing rooms, we did not go into the
rooms.

Point to be improved:
Classification, flows and pressure difference of the corridor used to access to the
manufacturing plant have to be reviewed and clearly described. (Necessity to add some
airlocks to be studied).
2 2. .3 3. .1 1 C Cl lo oa ak kr ro oo om ms s
Before going through the production area, we have to go first through the civil cloakroom
then through the clean one.
The gowning/de gowning SOP are clearly displayed in the cloakrooms.
2 2. .3 3. .1 1 W We ei ig gh hi in ng g A Ar re ea a
The weighing area, well designed (Material airlock and personal one), is equipped with a
laminar flow and 4 balances with different weighing scales.

The good practices are followed and clearly documented:
only Plastic pallets are used in clean area
100 000 classified Area
10 000 classified Area
Efficient extraction to protect the operator
Weighing sequence complies with the current standard (API: last material weighted)
ERP weighing recipe only the approved material could be used
Double checking (human and ERP System)
Strict requirement for weighing.

2 2. .3 3. .2 2 W Wa as sh hi in ng g A Ar re ea a
The washing operations are done manually.
All the material is dried using clean compressed air (0.22m filter).
The washed material is stored into the cleaned process rooms.
The cleaning status is valid for 14 days (validation performed previously).

Point to be improved:
It could be convenient to indicate where the dirty material is stored in the washing room
before cleaning.
The hoses have to be clearly identified to ensure the cleaning traceability and status.
The sink is damaged and have to be replaced.

Page 6/23

2 2. .3 3. .3 3 G Gr ra an nu ul la at ti io on n
CIFARMA is working with the High Shear Mixer Fluid Bed Dryer technology.
EQUIPMENT SUPPLIER MODEL
HSM FREWIIT MG 400/A
HSM GLATT WSG-UD 60
FBD GLATT
FDB GLATT
2 2. .3 3. .4 4 C Co om mp pr re es ss si io on n
The CIFARMA Plant is equipped with 7 tablets press machines.
EQUIPMENT SUPPLIER MODEL
Tablet Press TALLERES SANCHEZ D-27
Tablet Press KORSCH EK II
Tablet Press MANESTY D4
Tablet Press MANESTY B3B
Tablet Press RIVA CIII
Tablet Press KILLIAN PRESCORTER III
Tablet Press STOKES B-2

The IPC are performed every 30 minutes.
Each compression room is equipped with the relevant IPC measurement equipment (Scale,
hardness tester, thickness tester).
Following the CIRARMA policy, each compression room is equipped with a deduster and a
metal detector machine to ensure the tablet quality.
2 2. .3 3. .5 5 I In n P Pr ro oc ce es ss s S St to or ra ag ge e A Ar re ea as s
There is only one dedicated room to the IPS.

Point to be improved:
The surface dedicated to the IPS is not sufficient.
During the audit, we observed some cleaned containers and some bulk material containers
for trials into the IPS.
The organisation has to be revised and only the products waiting for processing have to be
stored temporarily into the IPS.
2 2. .3 3. .6 6 C Co oa at ti in ng g
For the moment, the coating and polishing solutions are prepared in the Coating room and
following the GMP policy (only one product per room).
With the current workload the design of the area could be acceptable but if workload
increase in the futures, it could be then convenient to dedicate a room for the solution
preparation operation to avoid any mix up or cross contamination issue.
Following the CIFARMA policy, the coating solution has to be used within 24 hours.

Page 7/23

EQUIPMENT SUPPLIER MODEL
Equipment Supplier Model
Film Coating machine WALTER BRUCKS 8
Film Coating machine R.MORANDI S/M
Film Coating machine WALTER BRUCKS 8
Sugar Coating machine MORANDI S/M
2 2. .4 4 PACKAGING
For the solid dosage form CIFARMA is equipped with 2 blistering machines and 3 secondary
packaging lines (manual operation).

EQUIPMENT SUPPLIER MODEL
Equipment Supplier Model
Blistering Machine FABRIMA BP-5
Blistering Machine GAMMA 010-81
2 2. .4 4. .1 1 P Pr ri im ma ar ry y P Pa ac ck ka ag gi in ng g
A - Design and workflow
The design of primary packaging area is satisfying:
The clean corridor is in over pressure compared to the blistering room
Blistering room in overpressure compared to the secondary packaging area
Pressure and ambient conditions data (temp less than 25 C and humidity less than
70%) controlled and registered (manometer and thermo-hygrometer calibrated)
Primary packaging is ISO 8 classified

Point to be improved:
HVAC qualification: Pressure difference to be clearly indicated and measured during the
qualification reference point for pressure measurement to be clarified.
When no operation is performed, the HVAC system of the area is stopped. Be careful about
the pressure inversion and the qualified status maintenance. A risk analysis has to be
performed as well as a qualification (documented) to ensure that the ambient conditions
remain compliant during the installation stopping.

B - operations
The operations are well managed and the good practices are followed:
100% of the blisters are checked by the in line camera. In case the camera is under
maintenance, 100% of the blisters are visually checked by the operators
Room status (product, batch number, date)
Packaging material is double checked before starting and before each material change
(alufoil roll, PM batch number)
IPC performed at the beginning, after each stop and every one hour (Leak test, Batch
number, expiry date)
Presence of the relevant SOP on line (line cleaning, operations)
Process well documented
Process and procedures knowledge
No wood pallets in first packaging area

Page 8/23

Point to be improved:
The packaging line cleaning SOP has to be more detailed (checklist to be implemented,
pictures to be added) to ensure the correct and reliable cleaning of the packaging line.
There is no de blistering SOP in place.
The HVAC System is stopped in case no operation is performed during the night, the week
end. This status is not qualified and no risk analysis has been performed. We request
CIFARMA to evaluate and document the possible impact like temporary pressure inversion,
room cleaning status
2 2. .4 4. .2 2 S Se ec co on nd da ar ry y P Pa ac ck ka ag gi in ng g
CIFARMA follows the good practices:
Physical separation between the line
one product per line/area
line status (product, batch number, date)
100% of the blisters are visually checked
Pack material checking before using
Inkjet printer tested before production starting
IPC performed at the beginning, after each stop and every one hour (Presence of the
relevant quantity and material, Batch number, expiry date, weight checking)
Material Reconciliation at the end of the operations
2 2. .5 5 LABORATORY
The laboratories are divided into 3 main parts:
Physico-chemical laboratory
Microbiological laboratory
Stability studies
2 2. .5 5. .1 1 P Ph hy ys si ic co o- -c ch he em mi ic ca al l l la ab bo or ra at to or ry y
The good practices are followed and clearly documented:
All the technicians are equipped with the relevant personal protection equipment
Analyses management using the SAP software
Calibration program in place and followed
All the preparations are clearly identified and dated
Presence and correct using of logbooks
Traceability of the solution, instruments used
Retain samples stored in a dedicated area (temperature controlled) till the expiry date
+ one year
Analytical standard storage (Temperature follow-up and presence of a backup)
Laboratories well equipped and maintained (cf. non exhaustive list below)
EQUIPMENT NUMBER TRADEMARK MODEL
HPLC 2 AGILENT VWD-RID 1100 &
1260
HPLC 3 MERCK HITACHI LACHROM ELITE
GC 1 VARIANT 430-GC
DISSOLUTION
EQUIPMENT
1 SOTAX AT7 SMART
DISSOLUTION
EQUIPMENT
2 VANKEL VK 7000 & 7010
TOC 1
SCALES METTLER TOLEDO


Page 9/23

Points to be improved:
The solutions are not kept waiting for the analysis results. In case of OOS, it is then not
possible to investigate on the solution. Analytical standard management (for VASTAREL) to be
revised to avoid any stock breakdown.
2 2. .5 5. .2 2 S St ta ab bi il li it ty y s st tu ud di ie es s a ar re ea a
CIFARMA is able to perform stability studies under conditions for the following areas II, IVa
and IVb (25 +/-2 C; 65+/-5% - 30 +/-2 C; 75+/-5%).
Till now, no stability studies have been performed for the SERVIER Products even for the
product fully manufactured locally.
Even if it is no required by the local authorities, we consider important to perform, on at
least one batch per year, some on-going stability studies. It would help a lot discussing with
local authorities in case of any quality issue.
2 2. .6 6 UTILITIES
2 2. .6 6. .1 1 H HV VA AC C S Sy ys st te em m
The qualification of the system is subcontracted to an external company and documented.

Points to be improved:
Plant drawing pressure difference and HVAC qualification report are not coherent.
CIFARMA has to clearly indicate their requirements and update the relevant documents in
consequence.
At the same time, the air flow (clean corridor, liquid plant concept) should be revised as
well as the relevant documents.
2 2. .6 6. .2 2 P Pu ur ri if fi ie ed d W Wa at te er r S Sy ys st te em m
The purified water specification complies with the standard.(conductivity less than 1.3 S)

Points to be improved:
A loop and plant sanitation has to be performed every 2 days to stabilize the purified
water quality (conductivity and microbiological growth). This situation is abnormal
A working group / project team has to be implemented to analyse the possible causes and
find the origin and solve as soon as possible this issue that could impact the product
quality.


Page 10/23

I II II I. . Q QU UA AL LI IT TY Y R RE EV VI IE EW W
3 3. .1 1 MANUFACTURING AND ANALYTICAL FILES REVIEW
3 3. .1 1. .1 1 B BM MR R/ /B BP PR R
The BMR (Batch Manufacturing Record) and the BPR (Batch Packaging Record) of the following
products have been revised:
Diamicron MR 30 mg batch 1102481 22/11/2011
Arcalion batch 10708900/10702790

It has not been possible to review a Diamicron 80 BMR due to the fact that the files are kept
on site only 6 months before being stored in another building outside the factory.

The level of information in the BMR and BPR are satisfactory.

Page 11/23

Points to be improved:
Arcalion:
P3/13 There is no cleaning certificate for a container used in production.
P3/13 The product residual humidity is measured using halogen equipment following the
following parameters; 2g 105C during 5 minutes (currently the specifications are given
for 5 g at 90C for 10 min)
There is no intermediate yield calculation (granulation, compression). This data is
compulsory to first follow up the production and the waste and overall to adjust if
necessary the quantity of Talc or Magnesium stearate (dilution and homogenisation step).
P6/13 The adjustment limits and rejection limits in compression have to be revised (the
standard ones for Arcalion are: Adjustment limit = +/- 1.9 % and rejection limit = +/- 2.6%)

Note: the temperature storage condition indicated on the Box and in the leaflet is: to store
below 30C.
3 3. .1 1. .2 2 A An na al ly yt ti ic ca al l F Fi il le es s
The analytical files are complete and well documented.

Points to be improved:
No analytical transfer neither analytical method validation have been performed for the
SERVIER Products.
In case of products packed locally, the analytical transfer could be enough.
For the products manufactured locally, an analytical method validation is required by the
local authority.
3 3. .1 1. .3 3 S St ta ab bi il li it ty y s st tu ud di ie es s
We recommend CIFARMA to perform on at least one batch per year some on-going stability
studies to be able to argue in case of Quality Issue with a product.
3 3. .1 1. .4 4 P Pr ro od du uc ct t S Sh he ee et t
The product sheets will be forwarded by CIFARMA and GRUNENTHAL within the next 4 weeks.
(Template in Annex 3)
3 3. .1 1. .5 5 A An nn nu ua al l s sa am mp pl li in ng g
SERVIER France is performing a complete full sampling of each product manufactured by its
partners. Within this context, CIFARMA will have to send to Ms Christel COCHIN 905 route de
SARAN 45520 GIDY FRANCE a complete box of each product processed and packed locally
every year since March 2012.
3 3. .2 2 QUALITY SYSTEM
3 3. .2 2. .1 1 S Se ee e a an nn ne ex x
Points to be improved:
Pharmaceutical contract CIFARMA:
The contract has been signed on February 15
th
, 2007. An update should be done within
the next weeks on GRUNENTHAL Peruana demand
The packaging yield for VASTAREL MR detailed in the contract is different from the BPR
documents to be updated

Product Release:
Abbreviation used in the document that are not detailed/explained in the general
glossary
Complaints G21 V10 from 19.04.2011:
In case CIFARMA receive a patient complaint, the industrial customer (GRUNENTHAL)
has to be informed within 48 hours (and not within 12 days as indicated in the SOP).

Page 12/23
3 3. .3 3 CONTRACT
A quality agreement has been signed between CIFARMA and GRUNENTHAL PERUANA that
defines the pharmaceutical responsibility.
3 3. .4 4 GMP CERTIFICAT
CIFARMA granted in January 2012 the GLP and GMP certifications from the local authority (cf
the enclosed documents).
CIFARMA is the first Peruvian pharmaceutical laboratory to get the GLP.
I IV V. . C CO ON NC CL LU US SI IO ON N
I would like to thank you for your welcome and your professionalism.
The audit has been conclusive and we confirm that CIFARMA comply with the SERVIER
requirements for manufacturing and packaging operations for the local market.
As agree, CIFARMA will propose SERVIER (IDPT) a CAPA within three weeks after report
sending.


Page 13/23
A AN NN NE EX X 1 1: : Q QU UA AL LI IT TY Y C CH HE EC CK KI IN NG G



Page 14/23













Page 15/23
Page 16/23

A AN NN NE EX X 2 2: : A AC CT TI IO ON N P PL LA AN N

N
U
M
E
R
O

REFERENCIAL AREA/ASUNTO PUNTO A MEJORAR CRITICIDAD
FECHA DE
AUDITORIA
ACCIN RESPONSABILIDAD ACTOR
FECHA
LIMITE
1 GMP 10.1 Almacn
Programa de control del almacn debe
aplicarse.
Mayor 30/01/12
2 GMP 10.1 Almacn
La puerta del almacn debe estar
siempre cerrada.
Menor 30/01/12
3
GMP 10.1 &
GMP 7.4
Almacn
Las condiciones de almacenamiento de a
granel importado deben ser respetadas.
Mayor 30/01/12
4 GMP 5.3 Almacn
Programa de calibracin de la bscula
debe ser revisado.
Mayor 30/01/12
5 GMP 4.1 Edificio
Revisin de diseo y clasificacin del
corredor de acceso a la fabricacin.
Menor 30/01/12
6 GMP 4.1 Edificio
El material sucio tiene que ser
almacenado por lo menos en un rea
especfica dentro de la zona de lavado
(ya que no es posible almacenar en un
espacio dedicado)
Mayor 30/01/12
7 GMP 6.2 Edificio
Las mangueras usadas en el rea de
lavado y fabricacin deben ser
identificadas claramente para garantizar
su trazabilidad.
Menor 30/01/12
8 GMP 5.2 Edificio
Lavabo de la zona de lavado daado y
debe ser sustituido.
Menor 30/01/12
9 GMP 4.1 Edificio
IPS no es suficiente y no se utiliza
correctamente (recipientes limpios
almacenado en el IPS)
Menor 30/01/12

Page 17/23
N
U
M
E
R
O

REFERENCIAL AREA/ASUNTO PUNTO A MEJORAR CRITICIDAD
FECHA DE
AUDITORIA
ACCIN RESPONSABILIDAD ACTOR
FECHA
LIMITE
10
GMP 4.2 & GMP
12.3
Utilidades /
climatizacin
Las especificaciones de requisitos de
usuario tienen que estar claramente
definido y climatizacin calificacin
protocolo y el informe debe ser
actualizado (diferencia de presin,
punto de referencia ...)
Mayor 30/01/12
11 GMP 12.3
Utilidades /
climatizacin
Para el ahorro de energa, el sistema de
climatizacin se para durante el periodo
de no produccin. El anlisis de riesgos
debe hacerse como calificacin para
garantizar el retorno al estado de
condicin de ambiente calificada
despus de un perodo de no
produccin.
Mayor 30/01/12

GMP 4.2 & GMP
12.3
Utilidades /
climatizacin
La diferencia de presin establecida
entre la planta y el informe de
calificacin de climatizacin no es
homognea.
Mayor 30/01/12

GMP 4.3 &
GMP 12.3
Utilidades /
PW
Ausencia de estabilidad de los
parmetros de agua purificada. Este
tema tiene que ser seguido con mucho
cuidado para evitar cualquier
contaminacin microbiolgica de
producto
Mayor 30/01/12
12 GMP 9.1
SOP /
documentacin
La lnea de embalaje hace aparecer SOP
que existe pero no est detallada - Lista
de verificacin debe aplicarse para
garantizar la capacidad de repeticin y
la eficiencia de la SOP
Menor 30/01/12
13 GMP 11.7
Laboratorio /
Solucin de
gerencia
En el caso de fuera de
especificaciones( OOS), soluciones
tienen que estar preparadas otra vez.
Nota 30/01/12

Page 18/23
N
U
M
E
R
O

REFERENCIAL AREA/ASUNTO PUNTO A MEJORAR CRITICIDAD
FECHA DE
AUDITORIA
ACCIN RESPONSABILIDAD ACTOR
FECHA
LIMITE
14 GMP 11.5
Laboratorio /
Estudios de
estabilidad
Como no existe un requisito local, no
hay estudios de estabilidad relacionados
con el producto de fabricacin en el
pas. Sin embargo, se recomienda
realizar estudios de estabilidad en curso
sobre al menos un lote por ao para los
productos fabricados por CIFARMA.
Nota 30/01/12
15 GMP 6.5
Aseguramiento
de la Calidad
Arcalion BMR Calculo de rendimiento
debe realizarse despus de cada
prctica para ajustar algunos
parmetros y la cantidad, si es
necesario.
Mayor 30/01/12
16 GMP 11.3 Laboratorio
Sin la validacin del mtodo analtico no
transferencia de anlisis se han
realizado.
Menor 30/01/12
17 GMP 6 Documentacin
CIFARMA enviara las hojas de
productos (product sheets)o las
informaciones adecuadas a SERVIER
dentro de las tres prximas semanas.
Nota 30/01/12
18 GMP 11
Control de
Calidad
Muestras a enviar al departamento DTPI
segn la demanda por e-mail cada ao.
Nota 30/01/12



Page 19/23

A AN NN NE EX X 3 3: : P PR RO OD DU UC CT T S SH HE EE ET T





Page 20/23








Page 21/23




Page 22/23



Page 23/23

A AN NN NE EX X 4 4: : G GM MP P C CE ER RT TI IF FI IC CA AT TE E