“Corrective Action” was the term first incepted by the US
Government during the second world war to address nonconforming material in
“Military Standard 1520”. Primarily, the focus of military standard was to
standardize the method on nonconforming material and their dispositions,
subsequently retitled as “Corrective and preventive action” (CAPA) and now
recognized to be a fundamental prerequisite in order to ensure healthy
functioning of “Quality Management system’.
CAPA’s requirement is well delineated in numerous ISO business standards as well as in GMP guidelines, such
as; “ICH-Q7 guidelines on Good manufacturing practice guide for active
pharmaceutical ingredients Q7 ” and “US-Food and drug administration department
of health and human services, 21 CFR Part 211-current good manufacturing practice
for finished pharmaceuticals”. However, the noteworthy concept of
“CAPA” emerge with the inception of “USFDA- Guideline on “Guidance for
Industry-Quality Systems Approach to Pharmaceutical CGMP Regulations released
in Sep-2006” followed by various ICH guidelines namely, “ICH-Q8 on
Pharmaceutical Development”, “ICH- Q9 on Quality Risk Management” and more importantly
“ICH-Q10 on Pharmaceutical Quality System” came into effective from June
2008.
CAPA is regarded a life cycle approach with the coverage of
all four phases of product as per “ICH-Q10 -Pharmaceutical Quality system
(PQS)”, in supplement to this, “USFDA- Guideline on “Guidance for
Industry-Quality Systems Approach to Pharmaceutical CGMP Regulations” describes
the CAPA as a well-known cGMP regulatory concept that focusses on
investigating, understanding, and correcting discrepancies while attempting to
prevent their recurrence.
CAPA’s Regulation for Pharmaceutical regulated
Industry:
- ISO 9001 & 13485: Quality Management System, clause
8.5.2 & 8.5.3.
- CDSCO-India: Schedule M- good
manufacturing practices and requirements of premises, plant and equipment
for pharmaceutical products, clauses 15.1 to 15.3 & 24.2.
- ICH-Q7 on “Good
manufacturing practice guide for active pharmaceutical ingredients”,
clause 2.41, 2.50, 2.51, 11.15 & 15.12.
- 21 CFR Part 211-current good manufacturing practice for finished
pharmaceuticals, clause 211.22 & 211.92.
- U.S.
Food and Drug Administration’s regulation governing medical device
manufacturers quality systems: 21 CFR Part 820.100.
- USFDA: Guidance for Industry-Quality Systems Approach to
Pharmaceutical CGMP Regulations, clause III- C & D , IV-D (4 & 6)
& glossary.
- WHO-Good
manufacturing practices for pharmaceutical products: main principles,
TRS-961, Annex-3.
- USFDA-Guidance
for Industry on “Investigating Out-of-Specification (OOS) Test Results for
Pharmaceutical Production”, clause Phase-I (b), Phase-II (a) & V.
- MHRA-Guidance
document on “Out Of Specification Investigations”, clause Phase-II &
III.
- ICH-Q8: Pharmaceutical development, clause- appendix-I (life
cycle management).
- ICH-Q9: Quality Risk Management, clause 1.5, I.3, I.5, II.4
& II.7.
- ICH-Q10: Pharmaceutical Quality System, clause 1.7 (f), 3.2.1
(a), 3.2.2 (Table-II), 3.2.4 (a) & glossary.
Helpful tips to develop an “Effective CAPA
system” – ‘3P Model’:
CAPA
is a fundamental management tool for Quality System demands the three essential
steps as illustrated per below Figure.-2 i.e.
effective CAPA system is all about the three stages; “3P- Plan, Process &
Product”.
Step-1 -“The Plan” – is to do an effective investigation in identifying the right
root cause:
In
general, plan is something begins with the end in mind as a product we desire,
our ultimate goal to achieve or destination to reach timely and successful
manner, which might results into the ineffectiveness or failure in reaching the
right destination first in time, if our map or plan is either not
available/clear and/or not detailed on “what, why, how, when and where to go?”.
Like-wise,
root cause analysis is the first key step in driving an effective CAPA process,
approach used for identifying the underlying cause (s) is to understand the
basics on how and why an incident occurred so as to conclude the most real root
/ proximate cause (s) of the problem.
Root
cause analysis is typically used when something goes bad and can be described
in asking below three basic questions:
What's the problem? This is a typical/problem statement as an outcome of
incidents/OOS etc.
Why did it happen? This can be answered by using the appropriate
tools to find out the causes.
What will be done to prevent it? This is typically resultant action points, called as
CAPA initiated based on the identified root cause analysis.
Establishing the why? By using appropriate RCA tools:
There
are several RCA tools (such as Cause and Effect Diagrams, Five whys, Cause
mapping, brain storming, Fault tree analysis, and failure mode and effects
analysis) are available and no single one is fit in providing the solutions for
all negative events. The applications and selection of tools comes from the
experience, situation and mainly the type of event occurred. Below two tools
are discussed here, which are used as most commonly problem solving tools for
day-in and out events happens.
Cause and Effect diagram (Fish-bone/6M tool):
“Cause
and effect diagram”, the tool was invented by Dr. Kouro Ishikawa and known as
Ishikawa diagram (also known as “Fish-bone” as its structure appears to be like
a fish), which connects the dots with the results obtained (called as symptoms)
vis-à-vis possible cause (s). This tool is most commonly used at the process
and manufacturing operations to provide deeper insight in breaking-down the
process into the secondary and tertiary causes so as to reach closer to real
and/or proximate cause (s).
5-Why’s Problem solving approach:
“5
Why’s?” is a pragmatic tool to ask “WHY”? And continue to ask until ascertain
the right answer on the “root cause of the problem”. The process involves the
discussion usually between the cross functional teams comprises with subject
matter expert, Manufacturing, engineering, Quality Assurance etc.
Step-2: “The Process”: CA (Corrective Action)
& PA (Preventive Actions) assessment and implementation.
An
anticipated road-map without converting into the actions has no value as long
as it is executed in alignment with the planner. Similarly, root cause analysis
has no meaning without converting into CAPAs?. Below is the chronological ways
in executing the CAPA’s “PROCESS” effectively.
Correction (Immediate Actions/Dispositions):
The
process of corrections includes to bring back the process or product into the
desired state or in some cases isolate the event to avoid further damages or
impact on the similar or potential product/processes, this may include “repair,
rework, or adjustment relating to the disposition of an existing discrepancy”
Corrective Actions (CA):
The
process is also known as CA (Corrective actions) begins with the actions
identified to eliminate the causes of an existing/detected
discrepancy/non-conformity or other undesirable situation to prevent
recurrence, below is the chronological process of CA:
- Defining
the problem or non-conformity, what?
- Define
the cause of the problem, why? i.e. RCA
- Developing
an action plan to correct the problem and prevent a recurrence? Identify-
CA
Implementing
the plan? Execute the identified-CA In specific, CAs are short, immediate
actions taken to “correct” or address the existing root cause (s) for each
reported deviation/ nonconformance. The actions are designed to eliminate or
minimize the potential for recurrence of the deviation/ nonconformance, which
are usually initiated (accountability in a formal quality system) or completed
prior to closing out of the investigation or proceeding with the next process.
CA
should be trended for the repetitiveness of same problem and its effectiveness
be tracked into the quality system with the category of events, examples may
include on equipment, product, process, material error etc.
Preventive Actions (PA):
The
process is also known as PA (Preventive actions) begins with the actions
identified to eliminate the cause of a potential discrepancy/non-conformity or
other undesirable situation to prevent such an occurrence, below is the
chronological process of PA:
- Define the potential problem or nonconformance?
What(Potential)
- Define
the cause of the potential problem? Why (Potential)
- Developing
an action plan to prevent the potential problem to avert occurrence?
Identify potential -PA
- Implementing
the plan? Execute the potential -PA
PA,
is the process for detecting potential problems or non-conformances' &
eliminating them, these are the longer term actions designed to determine the
effectiveness of corrective actions, which mainly focuses on to ensure the
“prevention” or occurrence of potential deviations/ non-conformances.
PA
should be trended for the repetitiveness of similar potential problem and its
effectiveness be tracked into the quality system with the category of events,
examples may include on equipment, product, process, material etc. PA are
required to be initiated or completed after closure of investigation or
corrective actions , which mainly focuses on the ‘system’s’ evaluations and
continuous improvement rather than quick fix-up.
Step-3: “The Product”: by ensuring ‘Effectiveness
check’.
Effectiveness
is the process of establishing something worth or degree to which something is
capable in producing a desired “Product”, specifically, “Averting the
same/similar problem” in future is the key objective in relations to ‘CAPA effectiveness
check’, this may include the verification of plan and process as mapped, how
did it work, followings can be considered as criterion to prove the
effectiveness:
- Ensure
the completion of CA V/s PA as planned.
- Effectiveness
of CA/PA can be based on predefined -number of batches versus period.
- Examine
the recurring issues, if any and why? Is it really due to this CA?
- While
it is subjective in terms of succession criteria as number of successful
batches , this may include further into micro level evaluation on to see
the degree of improvement as
- Is likelihood of event increased or decreased?
-Is the severity of the problem increased /decreased?
-Is any new hazard or harm detected?
Determine the impact of learning & succession curve with
mitigation plan. CAPA can be considered ineffective –fully or partially, if the
actions implemented has not produced the desired “Product” as expected to meet
pre-defined succession criterion, which further link to life cycle approach and
goes on back to start with the RCA again following the same 3P-CAPA model “Plan , Process
and Product” until the desired results are
obtained.
CAPA’s – Summary & Conclusion:
To summarize aforementioned discussions, CAPA tool is
employed in the entire life cycle of the processes, right from the birth to the
retirement of a product/processes, i.e. applied as a life cycle tool from
““product development, technology transfer to commercial manufacturing through
product discontinuation”. CAPA works begins in parallel to correct the existing
problem, while averting the similar potential problem resulting from the
investigations of complaints, product rejections, non-conformance's, recalls,
deviations, audits, regulatory inspections and findings, and trends from
process performance and product quality monitoring.
Effective
CAPA methodology results in continuous process improvements and helps in
enhancing the product and process understanding so as to make the systems and
processes robust in getting first time-right quality product.
Author: Sanjeev Kumar Singh
Deputy General Manager - Corporate Quality Assurance at
Mylan Laboratories Limited
www.gmpviolations.com
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