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PHARMACEUTICAL ENGINEERING
regulatory compliance
Risk-MaPP
www.PharmaceuticalEngineering.org
SPE developed a Baseline Guide, Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP),1 using a
scientific risk-based approach to maintain product quality and worker safety in order to reflect the importance
of quality risk management as defined by ICH Q9.2 Professionals with varied experience representing a number
of pharmaceutical companies in the US, EU and Japan
collaborated on the development of the Risk-MaPP
Guide. The content of the Guide was reviewed by the US
Food and Drug Administration (FDA) and acknowledged in
the forward section of the guide.
The Containment Community of Practice (COP) of ISPE
Japan Affiliate has been committed to the development and
the implementation of Risk-MaPP from the beginning.
In this article, some examples of the risk assessment
based on Risk-MaPP are provided for the prevention of
cross-contamination in solid dosage form manufacturing
facilities and summarized in the Appendices.
The four routes of cross-contamination indicated in RiskMaPP are listed below in order of importance:
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Risk-MaPP
Hazard Level
Exposure Route
Mechanical
Transfer
Airborne
Transfer
>10 mg/day
1 - 10 mg/day
0.01 - 1 mg/day
< 10 g/day
Open Process
Closed
Process
Long
Term
Short
Term1
10
Amount of
Airborne/Residue
Notes:
1. Short term means less than a few seconds. The scoring table
is based on the risk assessment table proposed in Baseline
Guide Bulk Pharmaceutical Chemicals (Second Edition).
2. In Table B, the scoring in case of MT cleaning limit at nonproduct contact parts is not defined. When containment system
do function well, the above case could not be considered.
Table B. Scoring of occurrence for process (example).
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7. Current Controls (Detection): scoring is based on characters of failures (e.g., carry over, upset, and leakage)
and its detection devise as shown in Table C. Failures are
classified into 1. failure that is foreseeable and avoided
beforehand by detecting its root cause, 2. failure that can
be detected when it happens, and 3. failure that cannot be
detected when it happens. Detection devices (automatic
vs. manual) provide easiness and reliability on detections
of failure and its root cause.
8. Risk Priority Number (RPN): RPN is a number obtained
by multiplying scores of severity, occurrence and detection. Limits or zones need to be established for RPN by
which acceptability and correction priority can be assessed.
Automatic
Detection
Manual
Detection
Detectable failure
(Not foreseeable)
Undetectable failure
10
10
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Risk-MaPP
Recommendations
In this article, the risk assessment methodology for GMP
(quality) concerns regarding cross-contamination, especially
airborne and mechanical transfer mode exclusively, was
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RPN is calculated by multiplying three scores: Severity, Occurrence, and Detection. When unsatisfactory
RPN numbers are obtained, the area of risk reduction
measures needs to be studied by examining these three
scores, i.e., the factors of the RPN.
The ADE is an important parameter in the assessment,
particularly in determining Scores of Severity in our
definition. Due to the fact that ADEs are scientifically
developed values, Scoring of Severity helps to add quantitative meanings. The ADE values established by different toxicologists should be sufficiently close so as not to
lead to different severity scores or control measures that
might be needed or implemented.
Verification data using the ADE applied over a standard
surface area (e.g., 100 cm2) consistent with the exposure
pathways used in the risk assessment need to be collected
to assess whether the risk reduction measures implemented as a result of the FMEA are adequate to control
risks to the patient.
3. Takahashi, H., and Nakamura, S., Case Study: RiskBased Approach to Containment and Control for Potent/
Hazardous Compounds, Pharmaceutical Engineering,
November/December 2009, Online Exclusive, www.
PharmaceuticalEngineering.org.
References
1. ISPE Baseline Pharmaceutical Engineering Guide:
Volume 7 Risk-Based Manufacture of Pharmaceutical
Products (Risk-MaPP), International Society for Pharmaceutical Engineering (ISPE), First Edition, September, 2010, www.ispe.org.
2. ICH Harmonised Tripartite Guideline, Quality Risk
Management, Q9, Step 4 version, 9 November 2005,
www.ich.org.
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