Vol. 5, Issue 10, October 2017, PharmaTutor, Paper-2
Vol. 5, Issue 10, October 2017, PharmaTutor, Paper-2
Vol. 5, Issue 10, October 2017, PharmaTutor, Paper-2
ABSTRACT
Quality Risk Management (QRM) is a key component for access the product quality. For any pharmaceutical
product, Quality Risk Management shall be applied to aim that raising the level of protection for the patient by
the reduction of the risk to which that patient is exposed at the time he /she receives a drug product. This
general objective can only be achieved by implemented policy of Quality Risk Management (QRM) on the
product and process design and its lifecycle.
The concept of risk management was first applied in the financial and insurance sectors. This concept was
systematically transferred and applied in the pharmaceutical industries in 2005 with the International
Conference on Harmonization (ICH) and its publication of the ICH guideline Q9 on “Quality Risk Management”.
The European Commission added this guideline as Annex 20 to the EU GMP guide in March 2008. This research
was explored the risk identification, risk assessment and development scientific risk control measures during
transportation of API from API manufacturing site to user site (formulation plant).
Key words: Quality risk management (QRM), International Conference on Harmonization (ICH), Failure Modes
and Effects Analysis (FMEA), Good Distribution Practices (GDP), Worst potential Effect, Contributory Factors,
Rate of severity, Consequences of failure, Probability of occurrence, Rate the effectiveness, Detection Control,
Degree of Risk Ranking
Methodology for risk Analysis and evaluation of risk in the supply chain transport:
By applying the FMEA tool and methodology the following aspects are evaluated to assess the risk and
evaluation of risk during transportation of API from API manufacturing site to user site (formulation plant site).
Determine which functions represent potential “Failure Modes” or points of potential failure.
Determine the worst potential “Effect” or consequences of each of the failure modes.
Determine the “Contributory Factors” for each failure mode
Identify any “Controls” in the transportation method / process. Controls are components of the process
which (a) reduce the likelihood of a contributory factor or a failure mode, (b) reduce the severity of an
effect, or (c) detect the occurrence of a Failure Mode or Contributory Factor before it leads to the
adverse outcome (Effect). Example of control measure is: Good Distribution Practices (GDP), validated
transport, Assign transportation controls and alarm systems for temperature excursion.
Rate of severity (consequences of failure) (S), Probability of occurrence (likelihood) (O) and rate the
effectiveness of each “Detection Control” (D) details is given in term of degree in the below table 1 “
Degree of Risk Ranking”.
Calculate the Risk Priority Number (RPN) as per below;
RPN = S x O x D
The product of three rating is the Risk Priority Number (RPN) for that Contributory Factor e.g. If severity
rating is 3, occurrence rating is 2 and detection level is 1, then RPN=3×2×1=6
Calculate the overall Risk Priority Number (RPN) by addition of each failure mode Risk Priority Number.
Calculate the Risk Assessment rating by assigning Risk Level (RL) as follows:
Sum of RPN for each failure mode
RL = ----------------------------------------------------------------- x 100
Sum of highest RPN for each failure mode (920)#
#
calculated as per highest RPN for each failure mode in table 1 degree of risk ranking
(5x5x5+5x5x5+5x5x5+5x5x5+5x5x5+5x5x5+5x5x5+3x5x3) = 920
API shall be chosen as per Risk Level Rating for consequences-
a) RL ≥ 70 %: Severe – API shall not be used for drug product manufacturing and supply is hold &
intimate to vendor for CAPA implemented
b) 50 % <RL <70 % : Major – Risk reduction shall be done additional control implementation during
transportation
c) 25 % <RL < 50 %: Moderate – Manage by routine monitoring process
d) Less than 25 %: Minor – No action required, risk is adequate and acceptable.
Risk assessment was carried out for API during transportation as per below table 2.
A case study, Aceclofenac BP is manufactured by the ABC Ltd. Gujrat and API supplied to directly XYZ Ltd.
Himachal Pradesh. The material has been transported through road permit with temperature controlled
container. As per BP monograph the storage condition of Aceclofenac is “Store in air tight container, protect
from light”. The accelerated and long term stability study was performed by the API manufacturer and shelf life
assigned for 4 yrs. Stress stability (mimicking transportation condition) study was not performed by the API
manufacturer.
SUMMARY
From the above evaluation of risk assessment based on FMEA it was summarized that the various critical steps
were expected to occur at each stage of supply chain, were adequate to reduce the associated risk. Methods of
risk management can be beneficially employed to identify, assess and control risk. It becomes clear that
potential risks change from one transport to the other. The result of a risk analysis can serve as the basis of
qualification of transport vehicles, transport packaging and supplier; they can supply important starting points
for the qualification of transport service providers or they can from the foundation of a monitoring concept.
↓ REFERENCES
1. World Health Organization WHO Technical Report series, no. 957, 2010 annex 5 WHO Good Distribution
Practices for Pharmaceutical Products
2. Information from European Union Institutions, Bodies, Offices And Agencies European Commission
Guidelines, 5 november 2013, On Good Distribution Practice of Medicinal Products for Human Use (text with
EEA relevance) (2013/C 343/01)
3. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use ICH Harmonised Tripartite Guideline Quality Risk Management Q9 Current Step 4 version dated 9
November 2005.
4. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use ICH Harmonised Tripartite Guideline Pharmaceutical Development Q8(R2) Current Step 4 version
dated August 2009.
5. EU GMP Guidelines on 19 march 2015 Principle of Good Distribution Practice of active substances for
medicinal products for human use.
6. A guide to supply chain risk management for the pharmaceutical and medical device industries and their
suppliers v.1.0 2010 the chartered quality institute pharmaceutical quality group website at www.pqg.org.