KAHIRA PHARM. & CHEM – IND.

‫شركة القاهرة لألدوية والصناعات‬

CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Risk Assessment Document For

Sterile Ampoule Facility

Page 1 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Table of Contents

1 Introduction..................................................................................................................................3
2 Aim of Risk Assessment..............................................................................................................3
3 Reference Documents/ Drawings................................................................................................3
4 Equipment/ System Description.................................................................................................3
5 Participants...................................................................................................................................4
6 Risk Management Process..........................................................................................................4
6.1 Identifying GMP risk.............................................................................................................6
6.2 Risk Analysis & Evaluation....................................................................................................6
7 Risk Assessment...........................................................................................................................8
8 Summary & Conclusion............................................................................................................38
9 Abbreviations.............................................................................................................................38
10 Revision History.........................................................................................................................39

Page 2 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

1 Introduction

According to the definition, given in Annex 15 to the EU-GMP-Guide, a Risk Assessment is a method to assess
and characterize the critical parameters in the functionality of an equipment or process. Therefore, risk
assessment is a key element in the qualification and validation approach.
In the project context, risk assessment for the equipment is performed as basic GMP/ EHS-Risk Assessment,
which shall help to identify important GMP/ EHS-requirements.

2 Aim of Risk Assessment

At the very basic stage of design the Risk Assessment is carried out to verify that all features are taken into
consideration to avoid the risk of failure of critical GMP and EHS parameter in the facility.
During study, all GMP, EHS and operational parameters will be identified and assessed for the risk, appropriate
mitigation will be proposed and verification point will be identified and defined.
The Risk Assessment report is produced to provide the documented evidence that design concepts or requirement
are complete in considering all GMP, EHS and operational risks.

3 Reference Documents/ Drawings

S.No.
Document Title Document Number

1. Validation master plan

2. Batch Manufacturing record
3. EHS SOP

4 Equipment/ System Description

The facility subjected to risk analysis is the “Sterile Formulation Facility” at Aseptic Ampoule area
The facility design is carried out after a detailed conceptual design complying with Schedule M (Egyptian
Drug Authority), WHO (World Health Organization), USFDA, EU-GMP and other international
regulatory agencies.
The building is designed in such a way that the warehouse, production, utilities, quality control, office area are
properly segregated to prevent cross-contamination between these areas.
The facility shall have separate entry for manufacturing and packaging area.
Material flow shall be linear in the facility according to manufacturing process, which is sequentially as
follows.
 Material Receive and storage
 Material dispensing
 Bulk manufacturing
 Product filtration
 Product filling & Sealing
 Automatic loading unloading

Page 3 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

 Manual visual Inspection with space provision for Automatic Optical inspection.
Secondary packaging
 Finished goods storage and dispatch
 Personnel entry is designed based on the cGMP requirement
Salient features of this facility
Following are the highlighted major features of the facility:
a) Conformance to cGMP and modern manufacturing concepts like:
 Material and Personnel flow
 Change procedures
 Flexible batch sizing
 HVAC system to support manufacturing activities.
 Purified water system complying USP
 Water for Injection complying USP
 Pure Steam complying USP
 Compressed air complying ISO specification
 Monolithic crevices free room finishes with epoxy.
 Efficient logistics and warehouse design.
b) The most modern manufacturing equipment with latest technology.
c) Latest automation for accurate and energy efficient operations.
d) Rich landscapes to minimize the dust pollution and enhance aesthetics.
e) In-house effluent treatment and strict compliance to pollution board norms.
f) Major emphasis on Environment, Health and Safety, (EHS) requirements.
.

5 Participants

Name Designation/ Department Signature/ Date

6 Risk Management Process

A typical Risk management process consists of following steps:

 Risk Assessment:
 Risk Identification
 Risk Analysis
 Risk Evaluation

Page 4 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

 Risk Control
 Risk Reduction
 Risk Acceptance

 Result of Risk management processes

 Risk Review

 Risk Assessment consists of the identification of hazards and the analysis and evaluation of risks
associated with exposure to those hazards.
Risk identification is a systematic use of information to identify hazards referring to the risk question or problem
description.
Risk analysis is the estimation of the risk associated with the identified hazards. It is the qualitative or
quantitative process of linking the likelihood of occurrence and severity of harm.

Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluation
considers the strength of evidence for all three of the fundamental questions.
The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of
range of risk. In case of qualitative description, the risk is expressed using descriptors such as
“high”, “medium” or “low”.

 Risk control includes decision making to reduce and/ or accept risks. The purpose of risk control is
to reduce the risk to an acceptable level. The amount of effort used of risk control should be
proportional to the significance of the risk.
Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a
specified (acceptable) level. Risk reduction might include actions taken to mitigate the severity and
probability of harm.
Risk acceptance is a decision to accept risk. Risk acceptance can be a formal decision to accept the
residual risk or it can be a passive decision in which residual risks are not specified.
 The output/ result of the quality risk management process should be appropriately
communicated and documented.
 Risk management should be an ongoing part of the quality management process. A
mechanism to review or monitor events should be implemented.
 The output/ results of the risk management process should be reviewed to take into account
new knowledge and experience.

 Risk management should be an ongoing part of the quality management process. A mechanism to
review or monitor events should be implemented.
The output/ results of the risk management process should be reviewed to take into account new
Knowledge and experience.

This document applies the risk management principles to identify the risks associated with the design,
Construction and operational features of the proposed sterile formulation facility.
The objectives of this risk assessment are to:
•Review the design around a structured methodology
•Identify the failure modes and associated risks
•Check if the proposed control measures are adequate
•Identify recommendations to obtain a more acceptable risk level if required

Page 5 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

7 7.1 Identifying GMP risk

Identification of Risk associated with the equipment, is generally based on prior experience and the concerns
of the participants of risk assessment document.

The risks identified are categorized as “GMP risk” or “non-GMP risk”.

GMP is defined as “the practices which ensures that products are consistently produced and controlled to the
quality standards appropriate to their intended use and as required by the marketing authorization.”

Thus, GMP covers all aspects of the manufacturing process: defined manufacturing process; validated critical
manufacturing steps; suitable premises, storage, transport; qualified and trained production and quality
control personnel; adequate laboratory facilities; approved written procedures and instructions; records
to show all steps of defined procedures have been taken; full traceability of a product through batch
records and distribution records; and systems for recall and investigation of complaints.

Thus, those risks which might have a direct or indirect impact on the quality of the product are classified as
“GMP risk”. Also, those risks which might result in regulatory guidelines non- compliance are also
classified as “GMP risk”.
For example: The Hygiene level of the manufacturing areas has a direct impact on the quality of the Product.
Thus, it is classified as GMP risk.
The “Non GMP” risks include risks related to EHS, operational and other non-critical hazards. Following

types of risks are mainly identified during risk assessment process:

 Risk related to hygiene level of the manufacturing and supporting areas

 Risks related to appropriate utilities and their control (eg. power source, compressed air etc.)
 Risks related to Automation
 Risks related to protection of the environment and health & safety of personnel.
 Risks related to cleaning, sanitization & sterilization
 Risks related to unidirectional flow of the material
 Risks related to cross contamination of the products
 Risks related to entry and exit of personnel and material.
 Risks related to all the environment features of the manufacturing areas.
 Risks related to requirement of particular rooms for different activities.
 Risks related to environment health and safety of personnel.

7.0 7.2 RISK ANALYSIS & EVALUATION

The risk analysis is performed using a qualitative basis of approach.

Qualitative analysis uses word form or descriptive scales to describe the magnitude of potential consequences/
impact and the likelihood that those consequences will occur.

Page 6 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

The qualitative measures of likelihood includes descriptors like “Unlikely”, “Possible” and “Likely”,
whereas the qualitative measures of consequence/ impact includes descriptors like “Minor”, “Moderate” and
“Major”.

Qualitative measures of likelihood

Level Descriptor Example detail description

1 Unlikely May occur at some time

2 Possible Might occur at some time

3 Likely Will probably occur in most circumstances

Qualitative measures of consequence/ impact

Level Descriptor Example detail description

 No impact on the product quality or outcome of the

1 Minor equipment.
 Features required for easing equipment operation.
 No direct impact on product quality/ outcome of
equipment. However, may indirectly affect the product
quality.
2 Moderate  Minor effect on personnel health
 Used in the initial stage of operation, however it may
affect the final output but those are not used for final
release of output.
 Effect on environment such as clean room.
 Features having direct impact on product quality/ outcome
of equipment like contact parts MOC, Surface finish,
Control system, Process air quality etc.
 Failure could lead to regulatory non-compliance.
3 Major  Loss/ damage to equipment or its critical sub-components
 Critical instruments not calibrated or not of desired range or
accuracy.
 Proper supporting documentation not provided.
 Major effect on personnel health
Based on the above parameters of likelihood and consequence a qualitative risk analysis matrix is
prepared to identify the overall Level of Risk, as mentioned in table below.

Qualitative risk analysis matrix – level of risk

Consequences/ Impact
Likelihood
1 – Minor 2 – Moderate 3 – Major
1 (Unlikely) Low Medium High
2 (Possible) Low Medium High
3 (Likely) Medium High High

The final Risk level shall thus be described using descriptors such as “Low”, “Medium” & “High”,
where each descriptor implies the following meaning:

Page 7 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Low – Risk can be accepted or ignored. These do not affect the final quality of the equipment/ system
and it can be managed by routine procedures and are unlikely to need specific application of
resources.

Medium – Risk required ongoing monitoring and review, to ensure level of risk does not increase.
Otherwise managed by routine procedures.

High – Action plans must be developed, with clear assignments of individual responsibilities and
timeframes.

8 Risk Assessment

In the following section a table is produced for the risk assessment. The significance or instruction for each
column is described in the following paragraph.

Column 1 : Serial number of the Risk assessment item

Column 2 : Process step/ Component: Identify the process step or component associated
with the risk.

Column 3 : Risks: Identify the type of risk associated with the process or component

Column 4 : Verify that whether risk have GMP impact in terms of Yes/ No.

Column 5 : Justification: Provide justification for declaring both Yes/ No for GMP impact in
column 4.

Column 6 : For the risk other than of GMP impact, write that what is/ are the type of risks
e.g. EHS, operational, etc.

Column 7 : Justification: Provide justification for considering the risk.

Column 8 : Risk level: Determine the risk level as High, Medium or low based on the
impact.

Column 9 : Risk Control: It is further divided into the following three sections:

Column 9a : Mitigation Method: Write the risk mitigation strategy as considered in the
design.

Column 9b : Residual risk level: After the risk mitigation what is the residual risk level,
whether it is Acceptable, Low or Medium.

Column 9c : Test document: Write the test point where the risk mitigation strategy will be
verified.

Column 10 : Status of RA: Mention the status of the Risk assessment point i.e. whether it is
‘Closed” or “Open”, after the execution/ approval of the Test document.

Page 8 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)

S.No. Risk Justification (5) Justification (7) Risk
steps/ Risk Risk Residual Test Status of RA
(1) (3) Level Mitigation Method (9a)
component Yes/ No type risk level Document (9c) (10)
(8)
(2) (4) (6) (9b)
Building and Regulations
 Based on the engineering
Weak building
calculations, Structural Building
Building Weak building construction:
1. No No impact on product EHS High designing shall be done and Low stability
strength strength Prone to damage
quality the construction shall be certificate shall
and personnel
carried out based on be provided
safety
structural designing. by Engineer
based on
 M30 concrete shall be
structural
used for providing the
design.
strength to the pillars.
Safety  Building construction Certificates
Building/ Facility
Statutory requirements should and NOC’s
2. not meeting the No No impact on product EHS are mandatory. High Low
Standards quality follow all local safety issued by the
required standards Complete safety regulation authority
of the applicable.
environment and  Height of the buildings
health of the and area coverage shall
personnel is be kept according to
statutory local statutory rules.
requirement.  All building material and
Utilities shall be designed
as per Egyptian Codes and
Standards.
 The building drawings
shall be approved by the
statutory bodies.
Site Master Plan
Necessary  Does not The master planning shall
EHS / Site Master
3. Master Plan Infrastructure to No NA comply with High be done considering: Low
Operational plan
support the safety norms like  Different buildings/ areas
production facility provision of for different activities.
has not been roads for
provided. movement of
Vehicles and

Page 9 of 41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
provision of  Separate Quality Control
pavements for lab consisting of both
personnel Chemical and
movement. Microbiology lab for
testing of RM, PPM, SPM,
 Reasonable
FG and in- process
distance
samples.
between various
buildings to  Safe distance between

maintain safety these buildings / areas.

norms will not  Roads to access all areas.
achieve.  Future expansion
 Future possibility provided so that
expansion on-going operations will
flexibility will not be disturbed.
hamper.  Proper drainage system to
 Proper co- avoid water clogging.
ordination of all  Roads, yards, parking lots
services in the etc. shall be paved with a
site for easy hard non dusting material
maintenance (like concrete etc.) where
will hamper. necessary
Warehouse
A separate warehouse area A separate warehouse area
No area provided in
with multiple rooms for shall be provided in the Facility
4. Warehouse the facility design Yes No NA High Acceptable
storage, is a basic GMP facility for storage of RM, qualification
for warehouse.
requirement. PPM, SPM and Finished
goods.
Receiving Receiving materials Using material from non- List of approved suppler
materials from unknown approved supplier which is should be available in the
supplier. a high impact on product No NA High receiving areas for all stores Acceptable SOP
5. Yes
efficacy & quality according to supplier
evaluation system

Page 10 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Sufficient space shall be

provided at unloading area,
wherein de-dusting shall be
performed using de dusting
tunnel.
 Sufficient area not  De-dusting tunnel shall be
provided for provided at Receive entry
staging & de- The external of raw material and PPM
dusting. contamination on RM/ and SPM entry and
Receive & Facility
6.
 No system Yes PPM/ SPM containers No NA Medium Receive area vacuum Acceptable
De- dusting provided for de- may enter the clean areas cleaner shall be utilized for qualification
dusting. of warehouse and de- dusting.
 Environment subsequently production.  Air tight door with air
contamination curtains shall be installed
may enter the at the Receive of the
warehouse area. warehouse, where the
material shall be unloaded.
 Pest control System shall
be provided for killing
insects and flies.
No designated A designated & clearly
Chances of mixing of
space allotted for marked space & racks shall Acceptable Facility
7. Quarantine Yes quarantine material with No NA High
storing quarantine/ be provided for quarantine/ qualification
approved material.
under test raw under test RM/ PPM/ SPM.
material.
No designated area Basic GMP requirement Reject RM/ PPM
is provided for so as to prevent chances of may get mixed A reject material store shall
Reject material reject RM, PPM or mixing of reject material Facility
8. Yes Safety with approved High be provided with lock and Acceptable
storage SPM storage. with approved material. qualification
material and may key arrangement.
be processed.

Page 11 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Primary No designated Separate storage area Separate locations with
Packaging storage area is for PPM is a GMP sufficient space shall be
provided for provided to store the Lay-out
9. Material Yes requirement. No NA High Acceptable
primary packaging primary packaging material
Store
material storage. in the warehouse area.
 The Primary Packaging
material shall be stored in
CNC (controlled not
The primary packaging classified) area with
Primary material comes in direct temperature control
Area is not a (<25˚C) and proper air Thermal
10. Packaging Yes contact with product, No NA High Acceptable
clean room. filtration. maps
material store hence should be stored in  The rooms shall be
a clean room. provided with proper AHU
supply and return air, with
temperature control.
No designated area Dedicated & defined
Secondary
provided for Separate storage area Lay-out
11. Packing Yes No NA Medium locations with sufficient Acceptable
for SPM is a GMP
material store secondary space shall be provided for
packaging material requirement storage of the secondary
storage. packing material.
No designated area Dedicated & defined
Raw material Separate storage area for Lay-out
12. provided for raw Yes No NA High locations with sufficient Acceptable
Store RM is a GMP requirement
material storage. space shall be provided for
storage of raw material.
Pallets/ racks shall be
RM/PPM/SPM Chances of damage/
Material provided for storage of
containers kept on contamination of the SOP
13. Storage in Yes No NA Medium material containers/ drums/ Acceptable
floors in the storage containers in case of any
storage shippers in respective
areas water/ solvent spillage.
areas dedicated storage areas.

Page 12 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) RA
component Yes/ No type risk level Document (9c)
(8) (10)
(2) (4) (6) (9b)
The Raw material shall be

stored in controlled area
(CNC area) with
temperature control
(<25˚C) & humidity control
(≤ 60%)
 The storage rooms shall be
provided with proper AHU
Raw material supply and return air, with
not stored under Some raw material needs temperature control
temperature- to be stored under Thermal maps
 Separate RM cold store
Raw Material controlled recommended controlled
14. Yes No NA High shall be provided for Acceptable
Store environment. temperature conditions or storage of temperature
 Area is not a else may degrade. sensitive raw material
clean room.
at 2 – 8°C.
 Temperature mapping shall
be carried out for the RM
cold store/deep freezer to
ensure temperature
uniformity.
 Routine temperature
monitoring shall be carried
out for RM cold store, as
per SOP
No segregation Physical demarcation shall
between Basic GMP requirement to
be required in respective
quarantine, under avoid chances of mixing
Material storage areas, so as to Lay-out
15. test & approved Yes of quarantine/ under test No NA High Acceptable
segregation segregate the quarantine,
RM, PPM and SPM material with approved
under test and approved
in their designated material.
material from each other.
storage areas

Page 13 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document (9c)
(8)
(2) (4) (6) (9b)
 A dispensing room
classified (C) with MAL
shall be provided in the
No area provided Separate dispensing room
Dispensing warehouse area for - HVAC
16. for dispensing of Yes of Raw material is a basic No NA High Acceptable
of RM dispensing of RM. qualification
Raw material. GMP requirement &
 Weighing booth (LAF - Weighing
should be classified (C)
class A) shall be provided booth
like preparation ampoule
inside the dispensing room, qualification
area.
wherein dispensing shall
be carried out.
Failed RM may  A separate sampling room
lead to failure in classified (C) with MAL
- HVAC
FP which may shall be provided for Raw
qualification
Sampling of raw material not meet Material Sampling.
No area provided - Weighing
is a basic GMP specified quality  Weighing booth (LAF
17. Sampling of for sampling of Yes Financial High Acceptable booth
RM requirement, for testing of and thus may class A) shall be provided
Raw Material. qualification
incoming material before lead to financial inside the Sampling room,
usage. losses. wherein sampling shall be
carried out.
Separate MAL shall be

provided for entry of Raw
Flow of material Material in sampling room.
Sampling & and man to the Different path for man and  Separate path shall be Lay-out
18. Dispensing sampling & Yes material entry to the No NA Medium provided for entry of Acceptable
area (RM) & dispensing area is sampling area is a GMP material to be sampled/
through same path. requirement. dispensed and exit of
PPM
dispensed/ sampled
material to avoid mix-up.

Page 14 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Finished goods storage area
No area provided in with sufficient space and
Basic GMP requirement to pallets shall be provided in
the warehouse for
19. Finished goods store all finished goods in the warehouse area for Facility
finished goods Yes No NA High Acceptable qualification
Storage the plant itself unless storage of finished goods
storage prior to
tested and approved. before approval and
dispatch.
dispatch.
No segregation Basic GMP requirement to Physical demarcation shall
between under test avoid chances of mixing be done in FG storage areas,
Finished goods & approved and of under test, approved so as to segregate the under Acceptable Facility
Storage rejected FG in FG and rejected FG. test, approved and rejected qualification
20. Yes No NA High
storage area. material from each other.
Finished goods storage

21. Finished goods not Some finished goods need area shall be provided with
stored under to be stored under temperature control Thermal
Finished
temperature Yes recommended controlled No NA High (<25˚C) & humidity control Acceptable maps & SOP
goods storage
controlled temperature conditions or (≤ 65%).
environment. else may degrade.
 Routine temperature
monitoring shall be carried
out for FG Area, as per
SOP.
Separate path shall be
provided for transfer of RM
The transfer of RM Unidirectional flow is from RM store to
RM &FG and FG is carried required to prevent cross Facility
Yes No NA Medium production area and for Acceptable
22. transfer qualification
out through same contamination of FG with transfer of FG from
path. RM. & Lay-out
secondary packing area to
the finished
goods store and then
dispatch, so as to maintain
unidirectional flow of
material in the plant.

Page 15 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) RA
component Yes/ No type (6) risk level Document (9c)
(8) (10)
(2) (4) (9b)
No area provided Dedicated room for A separate Recalled goods
Recalled for storage of storage of recalled goods store is provided in the SOP
23. recalled finished Yes with lock & key No NA High warehouse for storage of Acceptable
goods storage
goods. arrangements is a GMP any recalled goods.
requirement.
The flooring of the

warehouse shall be made
24.  The floor of the of Industrial tiles/Kota
warehouse is not stone/ epoxy without any
cleanable. Frequent cracks or gaps.
Cleaning is a basic breaking of SOP
 Accumulation of
Floors Yes requirement to prevent Operational floor will Medium  Floor shall be made up of Acceptable
dust at corners load bearing material to
contamination. hamper
 Floor is not warehouse avoid cracks
loading bearing.  Coving shall be done at the
& production wall to floor joints, to
operation prevent accumulation of
dusts.
Operational areas in
warehouse shall be
Low visibility in Suitable lux level is designed for minimum Environmental
Light Yes required for comfortable No NA Medium 400 lux level, whereas non- Acceptable
the warehouse area operational areas shall be measurement
operation.
designed for minimum of
25.
300 lux.
 The walls in the warehouse
area shall be painted with
Cleanroom conditions in electrostatic paint/ epoxy
The walls of the area may be
26. paint to prevent particle Room Data
Walls warehouse is Yes compromised. Dust may No NA High Acceptable
shedding. Sheet
particle shedding. be transferred to the  Alternatively, GI powder
adjoining production coated panels may be used
areas. in the warehouse instead
of walls.

Page 16 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (10)
component Yes/ No type risk level Document
(8) (9a)
(2) (4) (6) (9b) (9c)
 Change rooms (CNC)
shall be provided at the
main production area,
RM/PPM Warehouse
entry for both men &
women, where persons
remove their street
Persons enter into garments and wear
Personnel warehouse area Contamination of storage protective plant garments SOP
27. Entry to without changing Yes No NA High Acceptable
area and material. before entering
warehouse their street clothes. warehouse area.
area
 Warehouse SPM,
packaging & FG store
should have provision of
both complete change or
for over gowning.
Production –Areas
Media fill Rooms/Walk-

Media fill ampoules In Incubator with
No Rooms are should be incubated at sufficient space and racks Media fill
28. Media Fill available to Yes specified temperature (30- NA NA NA should be provided. Acceptable
protocol
Room incubate the media 35º & 20- 25ºC) for  Temperature monitoring
fill ampoules checking the growth of & indication facility
microorganism. should be provided in
media fill incubator
room.
No day store room Transfer of  Staging room (day store)
provided in the material from shall be provided in the
production area for warehouse to manufacturing area for
staging of production during staging of RM.
Lay-out
29. Staging dispensed PPM, No No impact on product Operational batch processing Medium  Staging area shall also be Acceptable
RM & SPM quality. may take long provided with the
required for the time. Process may ampoule filling line &
batch be intermittently Ampoule filling line.
manufacturing. stopped.

Page 17 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Separate lines with separate
Business loss, as set of equipment shall be
Manufacturing of
different provided in the same
ampoules and Eye-
products cannot production facility for Facility
drops is not
30. Manufacturing Yes Material mix up Financial be manufactured. Medium manufacturing of Acceptable qualification
possible in the
ampoules and Eye-drops.
same facility.
 Closed Ampoule washing
machine shall be provided
The ampoules in which for proper washing and
Washing & Non-sterile & sterile product is to be subsequent drying of
Depyrogenati particle laden filled should be properly ampoules. Tunnel
31. Yes washed and No NA High  Depyrogenation tunnel Acceptable
on of closed ampoules are used thermal
ampoules for sterile product dehydrogenated, so as to shall be provided for study
filling. prevent product depyrogenation &
contamination. sterilization of ampoules
prior to filling.
 Double door steam
sterilizer Autoclave shall
be provided for
Non-sterile sterilization of all
accessories, accessories, garments,
Using non-sterile
garments, machine machine parts etc. which
accessories will Autoclave
32. Sterilization parts, 0.22µ filters, Yes No NA High are going to be used for Acceptable
contaminate the sterile validation
seals, etc, are used ampoule filling operations.
product and clean room cycles
inside the filling  A preparation room shall
environment.
area. be provided wherein, the
steam sterilizer Autoclave
shall be installed and the
components shall be
prepared and packed for
sterilization.

Page 18 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Separate washing room with
sufficient space shall be
provided for cleaning of
No area provided for used machine parts.
cleaning of machine Proper cleaning of machine
33. Washing parts prior to Yes parts is a pre-requisite for No NA High  Separate room shall be SOP
sterilization. sterilization. provided for holding/ storing Acceptable
of cleaned machine parts.
Contamination of  Clean air shall be provided
machine parts over the machine parts
during washing, Particulate contamination washing station.
holding or during  Ceiling mounted LAF shall
transfer to steam of machine parts may
also be installed at the
sterilizer for occur, which may unloading side of steam SOP
34. Post washing Yes No NA High
sterilization or indirectly have an impact sterilizer so as to prevent re- Acceptable
during loading inside on product quality. contamination of articles
sterilizer. after sterilization.
 Ampoule washing
 The quality of machine shall be provided
water used for with supply of PW and
Ampoule washing WFI for washing.
&, machine parts  Quality of water to be used
 Initial washing shall be
washing is not for washing should meet
Washing designed using recirculated SOP
35. appropriate. Yes GMP requirements. No NA High water, then with PW and
& drying Acceptable
 Compressed air  Re-contamination of final washing with WFI.
used for drying is articles is possible.
contaminated  Filtered (0.22 µm)
compressed air supply shall
be provided to washing
machine for drying of
ampoules/ampoules after
each washing step.
 Equipment Wash room shall
also be provided with PW
and WFI supply for initial
& final washing of machine
parts.
 PW and WFI qualification
shall be carried out prior to
usage to verify its quality.
 Routine in-process testing
of PW and WFI shall
also be carried out as per
SOP, to ensure quality.
Page 19 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process steps/ GMP Other Risk Control (9)

S.No. Risk Justification (5) Justification (7) Risk Status of RA
component (2) Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
Yes/ No type risk level Document
(8)
(4) (6) (9b) (9c)
A solution preparation

room class C shall be
provided inside
manufacturing area for
preparation of product
solution.
 Jacketed preparation tank
(s) of sufficient capacity
and fixed with mixer of
suitable range shall be
Facility is designed for
provided for manufacturing
Mixing of Preparation of manufacturing of liquid SOP &
36. Yes No NA High of product solution. Acceptable
product product solution not injectable for which liquid Lay-out
 Jacketed preparation tank
possible. solution needs to be (s) shall be provided with
prepared. sufficient required
components and
instrumentation, which are
required for product
manufacturing.
 Separate solution
preparation rooms shall be
provided for both Eye
drops line & ampoule line
with dedicated preparation
tank s, as per production
requirement.
No provision in
 LAF shall be provided over
the preparation Environmental preparation tank manhole
tank for adding cover to provide clean
contamination of product
Jacketed product. SOP
Yes solution may lead to environment for product
37. No NA High Acceptable
preparation tank  Product addition increase in initial bio- addition as well as for other
(s) carried out under
burden. connections.
open condition.

Page 20 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process steps/ GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
component (2) Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
Yes/ No type risk level Document
(8)
(4) (6) (9b) (9c)
An automated CIP system

with required
instrumentation shall be
provided for cleaning of
tank (s) of Ampoule line.
 PW and WFI line shall be
provided ampoule line for
Jacketed cleaning of preparation
tanks used for Residues of previous
preparation tank tanks through CIP system.
product product may be left over CIP
38. (s) manufacturing are Yes No NA High  The CIP system should Acceptable validation
in the tank. Product have provision for addition
not cleaned crosses contamination
properly. of Acid and alkali system,
possible. which might be required
for efficient cleaning of the
tanks.
 The cleaning process shall
be validated for all tanks.
 An automated SIP system
with required
instrumentation shall be
provided for sterilization of
all preparation tanks.
Jacketed
tanks used for The initial bio-burden of  Pure Steam supply shall be
preparation tank SIP
39. (s) product Yes the product solution may No NA High provided in both the tanks Acceptable
manufacturing are increase. Process out of rooms for sterilization of validation
not sterilized. validated procedure. tanks through SIP system.
 SIP process shall be
validated for all the mixing
preparation tanks.

Page 21 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Sufficient number of
change rooms shall be
provided for entering into
the Grade C areas.
 Gowning provision shall be
provided in the change
Personnel are required to rooms for personnel
No change rooms SOP
wear protective gown in entering change room.
40. Personnel at the entry to Yes No NA High Acceptable
the entry change room, as
entry Grade C areas  Area qualification shall be
per clean room
requirement. carried out to demonstrate
compliance to Grade C.
 Gowning philosophy shall
be followed as per Entry &
Exit SOP.
IPQA room with sufficient
No room provided space shall be provided
In-process checks need to inside manufacturing area,
for in-process
be done at every stage of with necessary instruments Acceptable SOP
checks of product
41. IPQA room Yes the production. No NA Medium for in- process testing of
at different stages.
samples.
The change A Change parts & Tool
parts, tool kit room with sufficient space
No room provided should be kept shall be provided in the
Change/ to keep the change in the production production manufacturing Lay-out
42. Spare parts & parts, tools etc Yes Use tools of external Eye- Operational area for Low area for storage of change Acceptable
Tool room required of all drops for sterile injection immediate parts & other tools, required
equipment. ampoule manufacturing installation, for production equipment.
rectification.

Page 22 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 Filling area garments shall
be packed autoclave
wrapping sheets.
Re-contamination  After unloading the
of sterile garments Re-contamination of garments shall be SOP
Sterile while transfer from No NA High Acceptable
43. Yes garments may take place. transferred to Sterile
Garments steam sterilizer Product contamination Garment cubicle in entry
Autoclave to filling possible. Change room using mobile
area entry change LAF or in a closed
rooms. container to prevent re-
contamination.
 Different set of change
No change rooms rooms shall be provided for
provided for The change room for entering into filling area.
entering into filling  The hygiene level of
Yes filling area class B should No NA High SOP
44. Personnel area or the change be designed as per GMP change room shall be Acceptable
entry room provided are requirement to prevent planned as per GMP
not as per GMP contamination. requirements i.e. from
criteria. CNC → Grade D →
Grade C→ Grade B.
 Sterile filtration assembly
No provision shall be provided for
provided for filtration of product
sterilization of Yes Product solution shall No NA High solution through 0.22µ BMR &
45. Product be contaminated. filters. Acceptable SOP
filtration product solution
Prepared in  Sterilizable grade filter
preparation tanks. shall be provided for
filtration of product
solution.
No provision  Holding tank (s) of
provided for sufficient capacity shall be
holding of sterile provided for collection and
Sterile product needs to be holding of sterile filtered
filtered product hold prior to filling, so as
Sterile product solution from the - BMR
46. from preparation Yes to maintain a buffer. No NA High preparation tank (s). Acceptable - Sterile
product tank, prior to
holding  Separate Holding room holding
filling. with separate holding tank time study
(s) shall be provided for
Ampoule and Eye drops
lines

Page 23 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
A LAF shall be provided

over holding tank manhole
cover to provide Grade A
No provision in environment for product
the tank for Environmental addition as well as for
adding product. contamination of product other connections.
Holding tank - BMR
47.  Product addition Yes solution may lead to No NA High  A separate Vertical LAF Acceptable - Sterile
(s)
or sampling increase product may be provided for holding
carried out under contamination and false providing Grade A time study
open condition. results during sampling. environment for sampling
or else vendor should
demonstrate Grade A level
till the sampling valve
level.
 An automated CIP system
with required
instrumentation shall be
provided for cleaning of
holding tank (s) of
Holding tanks used Residues of previous Ampoule line.
48. Holding tank for product Yes product may be left over No NA High  PW and WFI supply shall CIP
Acceptable validation
(s) manufacturing is in the tank. Product cross be provided for all holding
not cleaned contamination possible. tanks for cleaning of tanks
properly. through CIP system.
The CIP system should
have provision for
addition of Acid and
alkali system, which might
be required for efficient
cleaning of the tanks.
 The cleaning process shall
be validated for all holding
tanks.

Page 24 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 An automated SIP system
with required
instrumentation shall be
provided for sterilization of
all holding tanks.
Holding tank used  Pure Steam supply shall be
Holding tank for product Sterile filtered product SIP
49. Yes No NA High supplied to all Holding Acceptable
(s) manufacturing is may be re-contaminated. Validation
tanks for sterilization of
not sterilized. tanks through SIP system.
 SIP process shall be
validated for all the
Holding tanks.
0.22 µ Filtered Nitrogen

gas/air supply shall be
provided at the top of the
holding tank for transfer of
No provision sterile product from tank to
Sterile provided for Product cannot be filled the buffer tank on filling - BMR
50. transfer of sterile Yes No NA High machine. Acceptable
product in ampoules or ampoules. - Filter
transfer product from  Alternatively, centrifugal integrity
holding tank to pump could also be
filling machine provided for transferring of
sterile product solution.

Page 25 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
A separate Ampoule filling

room with Ampoule filling
& sealing machine shall be
provided for filling &
subsequent sealing of
product filled ampoules.
No provision
Product needs to be filled  A buffer tank of sufficient
provided for filling
51. Filling of product from Yes in ampoules for further No NA High capacity shall be provided
holding tank into use. on both the filling BMR
ampoules machines for maintaining Acceptable
required buffer during
filling and preventing fill
volume errors.
LAF (Grade A) shall be
provided over entire
Ampoule filling &
Product filling is stoppering, as well as on - BMR
Product contamination
52. Filling carried out under Yes No NA High Ampoule filling & sealing Acceptable - LAF
possible.
unclean machine to prevent validation
environment. environmental
contamination during
product filling.
Transfer The transfer of A mobile LAF shall be
of sterilized machine parts to provided for transfer of
machine the filling machine, sterilized machine parts,
parts, filters, garments to sterile Chances of contamination bungs, seals, garments, and
seals, garment cubicle of sterile articles and other accessories to SOP
53. Yes No NA High Acceptable
accessories, and other subsequently product subsequent area from
garments accessories to contamination. cooling zone.
from respective area
autoclave to (after sterilization
respective & unloading) is
room in carried out openly.
filling area.

Page 26 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 A steam sterilizer
autoclave shall be with
No provision sufficient capacity shall be
Ampoule provided for terminal
terminal provided for Some products filled in
terminal sterilization of Ampoules Terminal
54. sterilization Yes ampoules & ampoules No NA High at 121°C for 20 minutes. Acceptable
Sterilization of sterilization
needs terminal cycle
ampoules & sterilization.  Ampoules shall be loaded
ampoules. on trays and the trays shall validation
then be loaded in the
terminal Autoclave
sterilizer.
The material of Product contamination The product contact parts of Acceptable Machine
product contact may occur. No NA High all machines shall be made Qualification
Material of parts of equipment up of St.St. 316.
55. construction is not suitable, may Yes
react with product.
 Using printed ampoules
which not need labelling.
No provision for  Packing room with
labeling and Labeling is a basic GMP sufficient space and 2 BPkR
56. Packing secondary packing Yes requirement for providing No NA Medium packing lines consisting of Acceptable
of product filled product information to necessary instruments
ampoules and patient. such as cartooning
Ampoules. machine & taping
machine etc. shall be
provided for secondary
packing of ampoules.
Visual inspection rooms
shall be provided for both
Particulate matter Ampoule inspection. The
Particulate (black, white rooms shall have visual Facility
contamination particles & foreign Foreign material may
57. Yes No NA High inspection tables with black Acceptable qualification
in ampoules. pieces) may be have impact on patient’s
and white board for
present in the safety.
detecting any foreign
product filled particles in the product
ampoules. filled ampoules.

Page 27 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Packing Area
FG Storage in FG shippers are Chances of damage/ Pallets shall be provided for
packing area kept on floors in Yes contamination of the No NA Medium placing of FG shippers in Acceptable SOP
58.
the packing area. shippers in case of any packing areas.
water/ solvent spillage.
Production – General Points
The plant layout shall be
designed with a logical uni-
directional flow based on
the following:
Area/ Equipment Difficulty in  Process Operation
are not arranged to Yes Operational Handling the High  Material flow starting from
ensure Chance of cross process the Receive of raw Lay-out
59. Process flow Acceptable
unidirectional or contamination or mix up operations material/ components to
logical flow in the the production of finished
facility goods and its dispatch.
 Waste disposal
 Difficult to clean  Improper cleaning causes Following measures shall be
and maintain the contamination in the taken to ensure Cleanability:
manufacturing area; desired hygiene  The building material shall
facility. room specification may be non-fiber shedding,
 The cleaning not be achieved. non-absorbable type and
media is not  Reactive cleaning media clean room suitable.
compatible with can lead to deterioration  Building finishes with
building material. Yes of surface evenness No NA High coving, epoxy flooring and
 Building material resulting shredding of plastic emulsion painting SOP
60. Cleanability Acceptable
is absorptive in particles. for walls
nature.  Improper surface contour  Easy access to the walls,
can lead to difficulty in ceiling and corners for ease
 Equipment surface
cleaning and particle of cleaning.
is not suitable for  The equipment shall have
cleaning deposition.
smooth, crevice free
surface.

Page 28 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 The floor is not The production area floor

cleanable  Accumulation of dust on shall be smooth without any
the floor & corners– may cracks or gaps.
Production  Accumulation of contaminate product. No NA Medium  Floors shall be epoxying Room
61. dust at corners Yes Acceptable data sheet
area floor screed laid on concrete
 Damage to floor during
 Floor is not screed.
material transfer.
loading bearing  Epoxy screed shall be of
 Floor is reactive suitable thickness to prevent
damage.
Coving shall be applied at all
corners, floor-wall joints for
better cleaning.
 Ceiling not smooth.  Ceiling in clean room areas
 Duct/ Diffusers/ shall be smooth without any
Light cut outs not crevices.
 Accumulation of dust  All ceiling cut outs shall be
sealed properly. particles in gaps and
Yes No NA High properly sealed using silicon SOP
62. Ceiling  Ceiling – wall ceiling- wall joints. sealant. Acceptable
joints are not  Leakage of environmental  Coved skirting shall be
cleanable air through cut outs. provided on ceiling –
wall joints.
No provision for  Double Decker AHUs
fogging inside should be provided for
clean rooms Viable particle count may Grade-B area
increase; It may lead to  SOP shall be developed
Yes No NA High SOP
63. Fogging the product contamination for fogging as per time Acceptable
During filling & required during
manufacturing activities. qualification stage.
 Supply & exhaust damper
should be 100% open
during fogging

Page 29 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 The doors opening in clean
room areas shall be
designed according to
pressure zoning
 Door opening is i.e. it opens towards room
not according to  Door might remain open with higher pressure,
Yes due to pressure. Door closure
pressure zoning. wherever possible. Room
64. Doors Operational will need high Acceptable
 Reactive Door MOC  In areas where it is not data sheet
 Doors MOC is not
suitable. may cause area frequent possible, high strength
contamination maintenance door closure shall be
affixed.
 Doors shall be made of
powder coated steel
construction of clean room
finish
 All the area shall be
prepared taking in to
consideration the number
Leads to and size of equipment
The defined number of the difficulty in man/ based on the production
Insufficient area/ Yes activities cannot Operational material capacities target and Room
65. Room size size of process be / EHS High production cycle time Acceptable data sheet
movement;
rooms. accommodated in the Operation and  Adequate free space for
proposed area. maintenance operation and equipment
activity maintenance and man /
material movement shall
be provided.
Improperly  Separate technical area
installed equipment from clean areas,
(technical area is accessible from outside,
not separated from Insufficient shall be provided wherever
Equipment
clean area) & Contamination of workspace possible. Facility
66. installation Yes EHS
and operating
inadequate space processing area makes it prone to High  Availability of adequate
Acceptable qualification
for operation and accidents space around the
space
maintenance with equipment for operation,
respect to room cleaning, inspection and
layout maintenance.

Page 30 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
An air lock or pass box shall

be provided for scrap removal
from Production Area.
No exit route  Disposal of waste from the
provided for scrap factory is in accordance with
removal from No the requirement of Facility
67. Scrap removal production area. Yes Basic GMP requirement NA Medium Environmental pollution Acceptable qualification
 No control on
Control Board. & SOP
 Scrap removal SOP should
disposal of scrap/
waste. mention the exact route and
process of scrap removal from
the production area.
 Working area shall be
 In critical places lack of designed with sufficient
minimum illumination illumination i.e NLT 400 lux
may affect the process.  Inconvenient in operational area and NLT
Operational for the 300 lux in non-operational
Yes  Chances of contamination operator to High area. .
Illuminati Insufficient and / EHS Environmental
68. in clean room area due to work in less  Adequate natural or artificial Acceptable measurements
on system improper lighting improper lighting design. light lighting shall be provided
 Higher risk during visual  Chance of throughout the establishment.
inspection, data reading Accidents in  Adequate lightning shall be
and recording. hazard area provided in the process area
e.g. visual inspection area etc.
 Lights in clean room areas
shall be of flush fitted type
and sealed with silicon
sealant.
 The lights shall be replaceable
from above the false ceiling
 Accumulation of dust without compromising clean
Light fittings are not Yes No NA room environment.
particles. Environmental
69. Lights suitable for clean Medium  The light fitting within the Acceptable measurements
 Leakage from improper clean room shall be with
room conditions
light fittings. smooth surface, without any
crevices.
 Flame proof type lightning
shall be designed in hazard
area, if applicable.
 For Photosensitive product
halogen lamp or yellow
light shall be provided.

Page 31 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
 Windows in clean room
areas shall be flushed from
Windows are not Accumulation of dust in both sides with no ledges RDS
70. Windows Yes No NA High Acceptable
flushed. the crevices. or crevices.
 Double glazed windows
shall be installed in the
entire production area.
 Service  Service penetrations shall

penetrations through manifold/ pendants

through wall are and the joints shall be
Service not leak proof. Contamination of clean properly sealed with SOP
71. Yes No NA High silicon sealant. Acceptable
penetration  MOC of service room.
 The service penetrations
penetrations is not
shall be made of SS 304 or
suitable to clean
better.
room.
 Furniture may be Any furniture inside clean
particle shedding. room should be made of SS
 MOC may not Clean room conditions 304 or better material and
RDS
72. Furniture be resistant to Yes may be compromised No NA Medium the design should not allow Acceptable
decontaminating any dust accumulation.
agents
All building materials

shall be resistant to water.
Seepage in Moisture within the room RDS
73. Water seepage Yes No NA Medium  Proper water proofing Acceptable
the building wall can lead to fungal shall be been done in all
growth areas.
 Proper differential pressure
.i.e. NLT 15 Pascal shall be
designed between 2 rooms
Proper differential of different hygiene level
Manufacturing pressure should be HVAC
74. Production Yes No NA High and NLT 10 Pascal Acceptable qualification
areas not maintained in the between rooms of same
area
pressurized production facility to hygiene level.
prevent contamination  Air flow study shall be
conducted to demonstrate
differential pressure.

Page 32 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
In these entire blocks,

HVAC system shall be
designed to achieve
respective ISO class as per
criticality of operation.
 In addition, appropriate
supporting measures such
as change room, airlocks;
GMP complying water-
proof, non- absorbent,
Difficulty to maintain the cleanable Floors, walls and HVAC
75. Hygiene level Breach in the Yes desired class, temperature No NA High ceiling will be considered Acceptable qualification
system and RH conditions during design and
execution. BMR
 All product processing
activity shall be carried out
in their respective grade
areas as per defined
standards.
 Temperature and RH
conditions shall be
designed as per clean
room & product
requirement.
Utilities
76. Utilities Lack of utility Yes Realization of product to EHS / Basic process High Following utilities shall Acceptable Facility
be produced with desired Operational requirement be provided: qualification
quality is not possible  Chilled water
 Cooling water
 Plant Steam
 Electricity
 Purified Water
 Water for Injection
 Compressed air
 Nitrogen
 Pure Steam

Page 33 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Cleaning of Final cleaning is Yes For Sterile facility the final  PW &WFI generation &

product performed using cleaning should be distribution system shall

77. No NA High be designed and installed in Acceptable
contact parts unclean water. performed using purified
of machine. water & WFI only. the facility for cleaning of
manufacturing equipment.
 Required number of user PW P&ID
points of PW & WFI user WFI P&ID
shall be provided.
 PW&WFI generated shall
meet the pharmacopeial
specification
 All piped service pipe and
cables shall be clearly
labelled and pipes should
Labelling of Labelling of utility Wrong utility may High have proper directional
pipelines & cables Yes Safety SOP
78. pipes and Prerequisite for be opened flow arrows. Acceptable
cables inappropriate qualification  All labelling shall be in
English language and
according to project
standard.
 The drains in
manufacturing area shall be
optimum and drain points
facilitate cleaning &
sanitization.
 Sanitary type drain system
of adequate size shall be
 Unwanted drains designed for unit operation
provided in the Yes No NA High and to prevent back flow
manufacturing and/ or prevent insects & SOP
79. Drains area. May contaminate the area. rodent entering the Acceptable
premises.
 Drains are not
 Drain verification shall be
properly designed.
carried out during area
qualification.
 SOP for cleaning and
maintenance of drains shall
be prepared.

Page 34 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Page 35 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
Facility design shall

minimize the risk of entry
of pests by closing of all SOP
Easy entry of pest
80. Pest Control Yes Affect product quality EHS Health hazard High openings. Acceptable
into the facility  Pest control for the entire
facility shall be planned.
 Tightly fixed doors with
 additional drop seals at the
bottom shall be provided.
 Air curtains shall be
provided for entry from
outside environment to
plant.
 Insecticutor /UV lights,
rodent traps shall be
provided
 Compressed air generation
and distribution system
which would generate
required quality of
compressed air should be
installed in the facility, for
the required functions.
Dry compressed air is  0.22 µ terminal filters shall
required for product be installed at the
Dry compressed air compressed air inlet line to Acceptable qualification
81. Compressed Yes processing, drying of No NA High
is not available critical equipment, wherein
air equipment and equipment
operation it comes in contact with
product or product contact
parts.
 Compressed air system
qualification shall be
carried out to confirm
quality, before usage.

Page 36 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) (7) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
A separate filter cleaning

room with sufficient space
and required utilities (water
and compressed air) shall
be provided for cleaning of
 Filter cleaning Required for routine Pre- filters.
area not provided  Dedicated area should be
Yes cleaning of Pre-filters of No NA Medium
Filter cleaning in the technical HVAC system and LAF’s, provided for storage of SOP
82. station area. installed in the technical cleaned filters to avoid re- Acceptable
area, manufacturing areas contamination.
 Filter cleaning
 Filter cleaning station shall
room not and warehouse.
be installed in the Filter
classified. cleaning room for cleaning
of filters.
Sending  A separate garment
garments to washing room should be
external vendor, provided in the facility for
may require cleaning of general area
 No dedicated area No impact on product inspection of garments of production and
provided for No Financial Medium lab.
quality, as garments could & third party to SOP
83. Plant cleaning of plant be sent to any external ensure quality of  Washing machines and Acceptable
Garments (general area) and Operation
vendor for washing. al washing. dryer should be installed in
lab garments, Washing may the room.
also require  The room should be clean
huge capital and should have separate
cost. space for storage of
cleaned garments.
Safety
 All electrical sockets shall
be provided with dust
 Electrical sockets May lead to fire, proof spring cover.
Electrical are not dusting Accumulation of dust which can RDS
 All electrical cables shall
84. sockets proof. Yes inside electrical sockets EHS destroy facility High Acceptable
be grouted within
 Short circuit in including wall/floor.
electrical circuit personnel  Equipment intended for
casualty. outdoor installation shall
have minimum protection
of IP66 or NEMA-46

Page 37 of
41
KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Page 38 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

Process GMP Other Risk Control (9)
S.No. Risk Justification (5) Justification (7) Risk Status of RA
steps/ Risk Risk Residual Test
(1) (3) Level Mitigation Method (9a) (10)
component Yes/ No type risk level Document
(8)
(2) (4) (6) (9b) (9c)
May affect the
product
manufacturing
operations &
product quality.
 Affect the entire All electrical & lighting
Earthing & Improper & Operational process fixtures design shall be in RDS
85. Lighting No No impact on product High Compliance to Egyptian Acceptable
inappropriate / EHS operation as it is
protection quality standards & other statutory
design  Prone to any
kind of high regulation
electrical energy
generation
which can lead
to casualty.

Possibility of untrained Access controls shall be

Access Easy access for persons enter the technical Theft/ loss provided in the core areas SOP &
86. Yes EHS of High Acceptable Lists
Control into Trespassers area and main production area
the site property entry,
NFPA/ Egyptian codes and

other relevant standards
shall be considered in
Fire can destroy design of facility.
Fire protection Lay-out
87. Fire in the facility No No impact on product EHS the facility High  Fire hydrant system, fire Acceptable
system
quality including detection & alarm system
personnel and fire extinguishers shall
casualty be designed & provided in
facility.

Page 39 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

9 Summary & Conclusion

 The Risk Assessment was performed to establish the design of the facility so as to be compliant to
expectations of various national and international regulatory agencies.
 The critical risks pertained to GMP and other than GMP, were analyzed with justification and mitigation
procedures.
 For each recognized GMP-risk and other than GMP risks, necessary measures are defined. Organizational
measures, like SOPs, are also possible measures for special GMP-risks. The availability of these SOPs
will be checked during the performance of the OQ.
 The risks where conceptual procedures shall be employed, standard operating procedures (SOPs),
Preventive maintenance schedules, Certificates and related documents indicated as mitigation procedures
shall be ensured at respective test points
“It is concluded that the Risk Assessment performed for the facility will prevent the risk of failures of
product during manufacturing”.

10 Abbreviations

EU-GMP : European – Good Manufacturing Practice

EHS : Environment Health Safety
GMP : Good Manufacturing Practice
RA : Risk Assessment
NMT : Not More Than
SOP : Standard Operating Procedure
USFDA : United State Food & Drug Association
AHU : Air Handling Unit
PPM : Primary Packing Material
SPM : Secondary Packing Material
ISO : International Organization for Standardization
NFPA : National Fire Protection Association
SS : Stainless Steel
db : Decibel
DQ : Design Qualification
IQ : Installation Qualification
OQ : Operational Qualification
PQ : Performance Qualification
O&M : Operation and Maintenance
GA : General Arrangement

Page 40 of
41
 KAHIRA PHARM. & CHEM – IND. ‫شركة القاهرة لألدوية والصناعات‬
CO. ‫الكيماوية‬

RISK ASSESSMENT FOR STERILE AMPOULE (ASEPTIC & TERMINAL)

11 Revision History

Date Revision Reason for Revision

00 New Document

Page 41 of
41