Estrategias y medidas

técnicas para identificación

y prevención de la
contaminación cruzada

Daniel Ballarin OCT/2021

Head of Technical Office

Vice-President Spanish affiliate

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Objectives
• How the process is embedded into the QMS
• Case study to show:
• Use of data to assess occurrence

• How risk changes based on the exposure potential

• Inadequate cleaning verification

• Inadequate cleaning procedures

• What’s the upside – business, process, etc. advantages

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INDEX

➢ CONTAMINATION & CROSS-CONTAMINATION BEST PRACTICES

➢ CASE STUDY ON RISK ASSESSMENTS FOR CROSS

CONTAMINATION

➢ EJEMPLOS PRÁCTICOS

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Contamination & Cross-contamination
best practices

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Where and why did all this begin?
It all began in 2005, 16 years ago!
First we have to look back at some of the industry drivers that have influenced
us over the last 10 years, and have had a huge impact on our GMP texts about
cross-contamination risks in the last years:

• Many APIs – Increasing potency & toxicity

• Reducing scale of manufacturing – personalised medicine
• Increased complexity: Products & Processes
• Increasing novelty: Products & processes
• Pressure to start facility projects as late as possible
– Product development projects fail in late phase clinical
trials.
– Need to get into market quickly.
– Need to be able to implement process improvement &
efficiency.
• Squeezed profit margins
• Sustainability aspirations & targets

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Influences of cross-contamination control guidance
From all these, the following most influenced the
cross-contamination control guidance:
• Many APIs – Increasing potency & toxicity
• Reducing scale of manufacturing – personalised medicine
• Increased complexity
• Increasing novelty
• Squeezed profit margins

What firms found

• They seemed to be squeezed into more and more dedicated and separate
facilities. They didn’t want these unless there was a really good reason for
them.
• The language of the GMPs, bracketing attributes of products in a non
scientific way was an issue.

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 The problem clauses
Dedicated facilities must be available for:
Certain

Antibiotics

Hormones

Cytotoxics

Sensitisers

Clauses 3.6, 5.18, 5.19 & 5.20 in the regulatory guidance are the problem EU & PIC/S GMP

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 The problem clauses

Clauses 3.6, 5.18, 5.19 & 5.20 in the regulatory guidance are the problem EU & PIC/S GMP

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The problem clauses

Clauses 3.6, 5.18, 5.19 & 5.20 in the regulatory guidance are the problem EU & PIC/S GMP

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Segregated and dedicated facilities EU/PIC-S regulatory background
• Applies to:
– GMP pilot plant.
– Clinical scale Investigational Product manufacturing (IPs).
– Commercial scale manufacturing.

• Increasing need to handle potent entities.

• At the same time, an increasingly risk averse culture
in our industry.
Lack of clarity about degree of separation required:
– Separate building.
– Separate suite within common building.
– Isolation of process within common facility.

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EMA tries to fix the problem in 2005
• A concept paper was published in 2005. This announced
changes to Chapter 3.6 and 5.18 intended to remove the
existing ambiguity.
• Chapter 3.6 mentions, for example, "certain" products
that should not be manufactured in the same production
facility.
This implies use of a dedicated facility, but the actual
products covered are unclear.
• The text also mentions "exceptional cases"
without defining either these or the "certain"
products.
Industry, including Inspectors, were confused!
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• The lengthy discussion about this subject prevented the
revision of the guide from being completed on schedule
(2006/7).
• Due to the great interest, EMA published a progress
report on 9th January 2008 on the state of the revision.
• This report says that the GMP/GDP Inspectors Working
Group has reached consensus that there should be:
– A list of substances for which a dedicated facility is mandatory.
– Additionally a list would identify substances for which specific
risk-based arguments will be necessary to allow shared facilities
to be used.
– Here, the text does not give any further details.

• So the concept of an A & B list emerges.

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So, the key issues in 2008 were…
• A prescriptive list(s) or not ?
• Our regulators were still open to science-based
persuasion at this stage.
• What do the following mean?
– “Dedicated…”
– “Self-contained...”
– “Exceptional cases”… ”campaign working…can
be accepted”
• Does this only relate to facilities?
• Could it also be systems serving facilities e.g.
HVAC ?

All very unclear and messy!!!!!

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Risk based thinking
The 1st Edition of “Risk-Based manufacture of
pharmaceutical products” – A guide to managing risks
associated with cross-contamination. September 2010.

So called RiskMaPP.
Note: A 2nd Edition is already done (ICH Q9 Q R M).
• Gets away from lists.
• Requires application of scientific knowledge of ADI
(allowable daily intake), and assessment of the risk that
cross-contamination ≧ ADI could occur, and application of
mitigation measures to keep below this threshold.

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Acknowledgement
• Many of the images and
explanations included in this
presentation has been prepared
by member of ISPE’s Risk-MaPP
Task Team. They have been
utilised to ensure consistent
expression of the Risk-MaPP
objectives.
• Other slides expressing industry
practice and regulatory
experience are taken from the
authors international experience.

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 ISPE RiskMaPP
Decision tree to assist with Manufacturing and Sourcing decisions Compound X - cGMP/Regulatory focus

N Is there a specific requirement to handle in a dedicated facility? Y

Obtain cleaning val criteria N

Can cleaning be demonstrably
carried out to meet criteria? N Can the cleaning criteria be
feasibility met by some of the stages?
cost
practicability
Can the contaminated equipment
Y be isolated to prevent facility N
Y contamination?

Are there any other factors that Y Can these issues be resolved?
Could prevent the use of a Y
Multi-product plant?
facility standards
Y N
operational
business confidentiality Can only be in multi-product facility with dedicated equipment or
units. Can only be in
OPTIONS single product
N Can be in multi-
facility
product facility
Disposable Dedicated Dedicated unit
equipment for equipment for
given step given step
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1.The basic requirement
demands understanding
the X- contam risk,
severity, and applying
appropriate control
measures for all multi-
product facilities.

2.Default requirement.
Dedicated facilities are
required when:
- Operational or
technical measures
are inadequate.
- Toxicological
evaluation does not
support controllable
risk.
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3.Some broadening
of the basic
requirements to
separate technical
poisons from
medicines.

4.Some more
general
requirements,
including an element
of risk to the patient
can be the route and
duration of
administration of the
medicine.

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5.Identifies the
QRM role, and lists
some aspects to
consider

6.Broadens the
concept of
dedication and
segregation to
contact parts, and
specific zones
within a general
facility.

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Now we have the new EU GMP requirements
7. Useful guidance
section on the
Technical
measures you
might consider to
manage the X-
contam risk to an
acceptable level.

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8. Useful guidance
section on the
Organisational
measures you
might consider to
manage the X-
contam risk to an
acceptable level.

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9. A periodic
review of the
effectiveness of
the procedures is
required.

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Summary – separated and dedicated facilities – the new GMP requirements

• Strong new focus on Multi-product facilities.

• Separated and dedicated is the DEFAULT requirement
unless a proper risk assessment can determine
alternative measures to manage the risk can be
deployed.
• The science & technical based approach is:
– Knowledge of the toxicological risks from cross-
contamination agents.
– Understanding the cross-contamination vectors.
– Controlling the risk to an acceptable level.
• Periodic review of the effectiveness of the
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 CASE STUDY ON
RISK ASSESSMENTS
FOR CROSS
CONTAMINATION

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Embed into Quality Management System

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API Details (Note 31 products with 10 APIs)
API ADE OEL LOWEST Scenario 4 in Risk-MaPP Second
mcg/day mcg/m3 DAILY DOSE Edition
mg/day
Anti-cancer 170 10 50
Anti-epileptic 250 10 150
Anti-hypertensive 1 25 3 2.5
Anti-hypertensive 2 400 50 50
Anti-psychotic 1 830 10 1800
Anti-psychotic 2 280 40 50
Anti-psychotic 3 1000 185 200
Misc. Agent 9750 580 300
Opioid 50 50 25
Vitamin B3 4200 2300 4

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 Information and Data Needed for Risk Analysis
✓ Product list including ADE/PDE, process, maximum daily dose, API form, product
presentation
✓ Equipment list including what products are produced in which equipment
✓ Process Flow diagrams
✓ Floor Plan, Flow diagrams, HVAC diagrams, room pressurization diagrams
✓ SOPs
✓ Historical Data
✓ Cleaning results, pressure differential alarm log, data from other data gathering studies, regulatory
actions, audits, deviations, incidents, and change control log

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How Health Based Limits are used for Risk Assessment
Cleaning Limits
Potential for Airborne and Mechanical Transfer
Surrogate in Placebo

Drug in Drug
Ranking of Severity in FMEA and other risk ranking tools
✓ The Health Based Limit is a direct indication of the potential harm to patient using the scientific knowledge to
meet one of the primary principles laid out in ICH Q9

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Effect of adding safety factors

Note – Acceptance Limit (using HBEL)

A wide margin of Margin of

safety indicates Safety
a low risk of New Limit determined by adding
failure additional safety factors – such as
using 1/1000th for cleaning limit
A small margin
of safety Apparent Margin of Safety
indicates a
medium/high risk
of failure Data

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Hierarchy of Limits
Acceptance
Limits
Action
Limits
Based on
The HBEL Alert Limits

Process
Based on historical
Control
data and/ or
Limits statistical analysis
of the process

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Causes of Airborne Transfer

• Open systems Inadequate filtration

✓ By design
✓ Non-contained processes ✓ Inadequate maintenance
✓ Interventions ✓ Inadequate alarm/monitoring

✓ Cleaning Filter cleaning

✓ Upsets/ Accidents
Intake and exhaust proximity
• Pressure differential
✓ Loss of pressure differential

✓ Inadequate pressure differential

✓ Inadequate alarm/monitoring

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Emission – Exposure –
What is “emitted” from the Contact with the emission
process (hazard)

An emission is needed for an exposure to occur; an emission does not mean an

exposure will occur
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Gradient Studies
Use methods similar to Industrial Hygiene testing
✓ Samples taken in source room, corridor and destination room(s)

✓ Used to determine the likelihood of airborne and mechanical transfer by measuring the tendency of an API to
migrate and settle on surfaces

✓ The rate of sedimentation is used to calculate the potential exposure due to the openness of the process and
the duration of openness.

✓ Compare this value to the Health Based Exposure Limit to determine the risk of cross contamination by
airborne transfer

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Sample Results from Gradient Study

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Sample Results from Gradient Study

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Sample Results

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FMEA – Airborne Transfer
Process Potential Failure Effect of S Potential Cause O Current Control D RPN
Step Failure
Milling Loss of pressure Airborne 5 Door open – single door 7* Manually check gauge at 7 245
differential to corridor beginning of shift

*Based on pressure alarm log

Below is the assessment after remediation – addition of alarms in process room

Process Potential Effect of S Potential Cause O Current Control D RPN

Step Failure Failure
Milling Loss of pressure Airborne 5 Door open – single 7* Automatically alarms in 1 35
differential door to corridor process room

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Causes of Mechanical Transfer
✓ Open systems
✓ Movement of materials/equipment without decontamination and cover
✓ Inadequate flow within the wash room
✓ Inadequate order of washing equipment/room
✓ Inadequate separation of clean and dirty equipment
✓ Inadequate gowning procedures
✓ Inadequate maintenance procedures

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FMEA – Mechanical Transfer
Process Potential Effect of S Potential Cause O Current Control D RPN
Step Failure Failure
Compression Dirty Gown Mechanical 5 Inadequate Procedure 10* Procedure 10 500
not removed Transfer

* Since procedure is inadequate assume occurring all the time

Below remediation – procedure improved

Process Potential Effect of S Potential Cause O Current Control D RPN

Step Failure Failure
Compression Dirty Gown not Mechanical 5 Human Error – did not 5 Procedure 10 250
removed Transfer follow procedure

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Causes of Manual Cleaning Failures

✓ Inadequate cleaning limits/ limit of detection

✓ Inadequate cleaning procedure
✓ Inadequate verification
✓ Did not follow procedure

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Inadequate Cleaning Limits/ Limit of Detection
✓ Not health-based using ADE/PDE
✓ Limit of detection near limit
✓ Incorrect calculation for 1/1000th of low clinical dose
✓ Use of lowest dose manufactured rather than low clinical dose of product

✓ Use of lowest dose does not taken into account contraindications (i.e. pregnancy, pediatric, etc.)

✓ Failure to compensate for pediatric use

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Inadequate Cleaning Procedure
✓ Not enough detail
✓ How to clean – scrub, etc.

✓ direction/order of cleaning, duration

✓ what tools to use

✓ Detergent
✓ type and concentration

✓ Water
✓ type, temperature, amount

✓ Where are hard to clean areas

✓ Where to visually inspect

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Inadequate Cleaning Verification
API ADE LOWEST Lowest 1/1000th LCD
mcg/day DAILY Cleaning Cleaning
✓ Manual cleaning – validated with DOSE Limit Limit
verification yearly mg/day mcg/cm2 mcg/cm2
Anti-cancer 170 50 2.0 0.6*
✓ Routine monitoring visual only
Anti-epileptic 250 150 2.6 1.5*
✓ Visual range not determined. Literature
suggests 4 mcg/cm2 Anti- 25 2.5 0.13 0.01*
hypertensive 1
✓ Compounds in red require chemical Anti- 400 50 41 5.1*
analysis for routine monitoring hypertensive 2
Anti-psychotic 1 830 1800 11 23.9
✓ Compounds in green require
chemical analysis for routine Anti-psychotic 2 280 50 3.0 0.54*
monitoring if using 1/1000th for limit Anti-psychotic 3 1000 200 7.6 1.5*
✓ Compounds with * indicate a possible Misc Agent 9750 300 108 3.3*
need for more sensitive analytical
Opioid 50 25 264706 132353
methods since the limit is lower
using 1/1000th cleaning limit PharmaceuticalVitamin B3 4200 4 48 0.05*
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Did Not Follow Procedure

✓ Inadequate training
✓ State of mind
✓ Distracted

✓ Rushed

✓ Not feeling well

✓ Misunderstand what is to be done and why

✓ Inadequate supervision
✓ Ergonomics/dexterity

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FMEA - Retention
Process Potential Failure Effect of S Potential Cause O Current Control D RPN
Step Failure
Granulation Not clean to limits Retention 5 Inadequate verification 7* Visual inspection 10 350
Granulation Not clean to limits Retention 5 Inadequate procedure 7** SOP 7 245

* Assumed each product turn over since cannot detect

** Assumed each product turn over since procedure is inadequate

Below is an assessment if chemical analysis is used at product change over and SOP improved (detail
and verification of steps)

Process Potential Failure Effect of S Potential Cause O Current Control D RPN

Step Failure
Granulation Not clean to limits Retention 5 Inadequate verification 3 Chemical analysis 3 45
Granulation Not clean to limits Retention 5 Inadequate procedure 3 Improved SOP 5 75

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What are the advantages?

✓ A robust risk management system for cross contamination provides knowledge on the
products, processes, facilities and equipment to permit better and more informed decisions
throughout the organization
✓ The HBEL provides a value that meets the intent of ICH Q9’s requirement that the evaluation of
risk is based on scientific knowledge that ultimately links to the protection of the patient
✓ Using a hierarchy of limits allows processes to be monitored and corrected prior to failures
requiring full investigation
✓ Using HBEL based cleaning limits are conservative (even for low hazard compounds) and in
many cases will allow the continued use of visual inspection only for routine monitoring

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Key messages
✓ Risk is a function of hazard (the compound) and exposure (the process and controls)
✓ Hazard remains constant with the API and is characterized by the ADE/PDE

✓ The process/equipment/procedures are assessed to determine the potential exposure of one compound to
another

✓ Assessing how well the facility implements the GMP’s is an essential part of the risk
assessment process
✓ Use of data is essential to a robust risk assessment
✓ Cleaning is just one mode of cross contamination
✓ HBEL’s are used to set cleaning limits as well as for assessment of airborne and mechanical
transfer
✓ Embed the process into the Quality Management System to ensure it is a lifecycle approach

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Processes
Process: Sample, weigh, mill, granulate, mill, dry, mill, blend, compression, and pack (10 steps)

All processes are fairly open (i.e., there are no containment devices or engineering controls used)

The facility uses a matrix approach to cleaning validation so therefore the cleaning limit used as
the acceptance criteria for validation and routine verification/monitoring is 0.1 mcg/cm2. This value
corresponds to the lowest cleaning limit combination (Anti-hypertensive1 and Anti-hypertensive2)

The cleaning procedures are all manual based with only a visual inspection by the operator and a
supervisor to verify the equipment is cleaned to the limits (0.1 mcg/cm2).

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FMEA Scoring
Value Severity Occurrence Detection
10 Injury to a patient or More than once per batch Not detectable by current
employee; ADE< 1 mcg/day methods
7 Cause extreme customer Once per batch All manually inspected
dissatisfaction; ADE 1-10
ug/day
5 Something likely to result in a Once per 6 months Statistical sampling
complaint; ADE 10-100 Manual inspection with
mcg/day verification
3 Minor nuisance resulting in no Once every 1 – 3 years 100% inspection
loss; ADE 100-1000 mcg/day

1 Be unnoticed and not affect One occurrence in greater Obvious or controlled and
performance; ADE > 1000 than five years monitored and alarmed by
mcg/day control system

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RPN Action Ranges

RPN Range Risk Level Action

1000 – 343 High Cease until remediated
342 – 100 Medium Remediate – can continue operations
99 – 1 Low Monitor

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Causes of Mix-up

✓ Flow routes/lack of space for storage and WIP

✓ Inadequate verification of labeling
✓ Inadequate training
✓ Inadequate supervision
✓ Did not follow procedure

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FMEA – Mix-up

Facility Process Step Potential Effect of S Potential Cause O Current Control D RPN
Failure Failure
OSD Receiving Wrong Label Mix-up 5 Inadequate 3 SOP 7 105
verification
OSD Compounding Wrong Mix-up 5 Human Error – 5 Manual verification 7 175
Materials materials staged
in corridor

Note both items should be remediated

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K5
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n
n
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w
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ec
t
d
gi
en
g

Limit (mcg/cm2) = ADE(PDE)A x Batch SizeB Where MDD = Maximum Daily Dose
MDDB x SSA SSA – Shared Surface Area

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Contamination main factors

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Design Opportunities
The design of a facility, its Heating Ventilation and Air Conditioning (HVAC) system and equipment
is the first and critical step in preventing contamination and cross- contamination.

Relating Preventive Measures, the Facility must:

be of suitable size, construction and location to facilitate suitable cleaning, maintenance and
appropriate operation
have adequate space for placement of equipment as well as production and packaging materials
consider the sequence of operation during the design phase; paying particular attention to the
location of equipment and removal of unnecessary traffic
have adequate internal temperature, ventilation and lighting;
have smooth surfaces (no cracks, crevices or shedding), which are easily cleaned
have adequate segregation of materials products and components to further reduce the risk of
cross contamination.

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Design Opportunities

Equipment
All equipment should have smooth inert surfaces which are not additive or adsorptive, and installed in an
area that is easily cleaned.
If the equipment is difficult to clean, then consider using it for a dedicated purpose.

HVAC system
Airborne contaminants are controlled through effective ventilation and filtration. The criteria is detailed in
the next section, Effective Airflow/Extraction and HVAC Design.

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 Effective Airflow/Extraction and HVAC Design

External contaminants should be removed by effective filtration of the supply air, to retain the
required cleanroom classification.
Internal contaminants should be controlled by displacing the airflow:

• The Pressure Differentials should be of sufficient magnitude to ensure containment and

prevention of flow reversal without creating turbulence.
• If a Recirculation System is installed, the ratio of fresh air to recirculated air must be justified.
• Where possible, ventilation dampers and filters should be designed and positioned to be
accessible from outside the manufacturing areas for ease of maintenance.
• Directional airflow within production or primary packing areas assist in preventing
contamination.

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 Manufacturing Process
There are many opportunities for contamination of raw material, intermediates or packaging materials
throughout the manufacturing process.

To minimise risk of contamination and cross-contamination, the following should be considered:

• Dedicate the facility to the manufacture of a single formulation of product.

• Manufacture products in a campaign, with the appropriately qualified cleaning processes and checks
performed in-between batches to minimise the amount of product changeovers.
• Utilise a closed manufacturing system. This is where the product is not exposed to the immediate
room environment (and vice versa).
• Perform an area line clearance according to approved procedures following each cleaning process
and between each batch/campaign.
• Zone the facility.
• Use Cleaning Status labelling on all equipment and materials used within the manufacturing facility.

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 Personnel Training and Clothing
Training is key in instilling good practices in personnel, that is: knowing that each and every person has a
responsibility to consumer health. Each employee must understand their role and responsibilities, which
should be clearly outlined in a job description.
Prior to and during employment, all personnel should undergo the relevant GMP and cleaning training
and be periodically assessed for competency.
The importance of gowning should be implicit and competency of gowning/de-gowning procedures
should be clearly documented and routinely monitored particularly in sterile situations via
microbiological testing.

Personnel should wear appropriate clothing to the duties they perform and the environment they work
in. These include:
• Personnel protective equipment (PPE)
• Clean body coverings (refer to Figure 3: Basic GMP Gowning)
• Cleanroom clothing (appropriate for each cleanroom classification), which can withstand repeated
wear and laundering with minimal deterioration (refer to Figure 4: Cleanroom Gowning)
• Appropriate footwear (e.g.: steel-capped shoes and shoe covers), which is provided by the company.
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Gowning

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Gowning

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 Cleaning Procedures

Having inappropriate or ineffective cleaning procedures could invariably cause

cross- contamination between batches and/or campaigns. To minimise the risk of
contamination and cross-contamination, cleaning procedures must:
• be appropriately designed, taking into consideration the product formulation,
the equipment design and functionality of the system
• clearly documented and not be open to interpretation
• be validated to provide documented evidence that the procedure utilised is
capable of cleaning the equipment to the predetermined acceptance criteria.

The following lists some of the cleaning criteria for cleaning equipment and general
housekeeping.

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TAKEAWAYS____________________________
➢ It is critical that the facility, equipment and HVAC design allows for effective cleaning and
ensures cross-contamination is controlled. The facility and equipment should:

▪ be appropriately installed and qualified

▪ have effective cleaning procedures validated.
▪ have procedures documented in such a way as to ensure that each operator consistently
performs the task, leaving no room for interpretation.

➢ Regular training and revalidation testing will ensure methods are consistent and are adhered
to.

➢ Any non-automated cleaning methods should undergo more frequent testing.

➢ Failure to prevent contamination and cross-contamination may result in serious consequences

to the consumer as well as the company’s reputation.
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EJEMPLOS PRÁCTICOS

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Impacto
Pérdidas de
Beneficio

Relación con
Proveedores

Reputación

Regulatorio

Suministro

Paciente

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Ejemplos de contaminantes
Aceite Plomo Cristal

Tuercas y tornillos Asbestos Misc.

Monedas

Pintura Óxido Juntas Acero inoxidable

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Ejemplos de observaciones detectadas durante GEMBAs

• Riesgo de contaminación por materiales extraños (papel, cartón, plástico) en tamiz

• Herramientas depositadas en lugar inadecuado

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Ejemplos de observaciones detectadas durante GEMBAS

Riesgo de contaminación por equipo no contemplado en proceso de limpieza

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Ejemplos de observaciones detectadas durante GEMBAs

Riesgo de contaminación por material no certificado en contacto directo con

producto en mangas de unión y descarga.

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 Ejemplos de observaciones detectadas durante GEMBAs

• Riesgo de contaminación debido a partículas metálicas procedente de equipo deteriorado

• Riesgos de contaminación por silicona procedente de junta deteriorada y ajuste inadecuado

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 ¡Ahora tu!
¿Puedes identificar riesgos de contaminación fisica en los
siguientes casos?

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 Sin guantes Herramientas depositadas sobre bin
abierto

Puerta abierta

Conducto
sostenido
mediante cable
atado

Presencia de materiales de
desecho

¿PUEDES SEÑALAR LOS 5 RIESGOS?

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 Instrucciones
marcadas
inadecuadamente
Vibrador sujeto con bridas

Rotura de bin reparada de forma

inadecuada

¿PUEDES SEÑALAR LOS 3?

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 Reparación temporal con cinta
adhesiva

Accesorio
depositado sobre
tapa bin

Presentation title ¿PUEDES SEÑALAR LOS 2 RIESGOS?

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Marca la diferencia - Tolerancia cero a la contaminación
Todos debemos adoptar y sostenener
Tolerancia Cero a la Contaminación

Es necesario erradicar la contaminación

de raíz y no tratar de justificar cuáles
son los niveles aceptables.
Si detectas un potencial riesgo,
comunícalo de inmediato al Supervisor
del área para que tome las acciones
necesarias

Solo mediante un comportamiento

apropiado podemos minimizar el
riesgo para nuestros pacientes y
consumidores

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 ¿Cómo puedes TÚ ayudar a prevenir la
contaminación?
• Sigue los procedimientos (y desafía / plantea potenciales problemas si crees que el procedimiento
necesita mejorar)
• Mantén siempre un lugar de trabajo limpio y ordenado
• Pon más énfasis en la prevención durante auto-inspecciones
• Asegúrate de que estás vestido correctamente
• Si no estás seguro, siempre PARA y pregunta a tu responsable o supervisor
• Informa siempre de incidencias y fallos de equipo, no asumas que ya se ha abordado. Cuanto antes
identifiquemos la posible contaminación del producto, más posibilidades tenemos de minimizar el
impacto

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FUENTES:
• Contamination & Cross-contamination best practices – PHARMOUT

• CASE STUDY ON RISK ASSESSMENTS FOR CROSS CONTAMINATION – ISPE

• CROSS-CONTAMINATION IN SHARED FACILITIES – PICS

• White paper: Prevention of Contamination and Cross-Contamination in Medicinal

Manufacturing Facilities - PHARMOUT

• eGuide Contamination control in pharmaceutical industry LINDSTRÖM

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Muchas gracias

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