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INTRODUCTION
focus its resources rather than stubbornly applying effort on
In recent years, the Food and Drug Administration the less critical aspects of operations. This is especially true
(FDA)-regulated industry has been listening to agency rep- for operations such as the typical cosmetic, or Over the
resentatives and consultants talking about the need to im- Counter (OTC) drug site that manufactures hundreds of dif-
plement a risk-based approach to decision-making ferent products in fully flexible facility equipment set-ups
processes. I totally agree with the need to implement this with minimum resources, which permits them to compete in
common-sense approach, but my question is this: Is this their selected markets.
actually a new approach?
Industry personnel have been considering risk in every- SCOPE
day decisions, but have not realized or documented these
decisions properly. I think that the key issue here is formal In this article, I will describe a practical approach to ap-
documentation. In the future, the industry must focus on and plying impact and risk concepts to the processes and docu-
devote more time to pursuing and completing risk-related mentation related to facility systems and processing equip-
documentation. Firms must develop procedures to ade- ment qualifications within the cosmetic and OTC drug (top-
quately document risk-based decisions, estimate their criti- ical and oral) manufacturing segments. In addition, I will
cality, and evaluate their impact. The FDA is even imple- describe the procedural requirements and the documenta-
menting this approach internally for its inspection plans. tion needed to use impact and risk concepts during the def-
Another statement with which I totally concur reads: inition of the systems and equipment qualification require-
Risk management is nothing more than resource manage- ments. The article is not intended to describe the Risk As-
ment. Risk management is the process of identifying the sessment tools in detail, but to provide a guide for the ap-
critical areas on which each entity within the industry must plication of these tools.
4 I n s t i t u t e o f Va l i d a t i o n Te c h n o l o g y
Miguel Montalvo
Within the article, I will make reference to the Interna- POLICY AND PROCEDURE
tional Society for Pharmaceutical Engineerings (ISPE) im-
pact concepts from their Baseline Engineering Guides The first thing that a facility requires is a policy and pro-
specifically to Volume #5 on Commissioning and Qualifi- cedure document that defines the implementation of the
cation (see Reference 2). There are three different levels of chosen approach. The policy will include the scope and ob-
impact: direct, indirect, and no-impact. Following are their jective of the program, the personnel responsible for its im-
basic definitions: plementation, the steps in determining test requirements
based on impact or risk, and the documentation to be gen-
Direct Impact System equipment or system that erated as a result of the analysis (including the protocol test-
will have focused and immediate impact on prod- ing requirements). The procedure will establish the steps to
uct quality determine an adequate level of testing using the impact as-
Indirect Impact System equipment or system ex- sessment concepts and a risk criteria developed by the man-
pected to have incidental or secondary impact on agement team. Some of the decisions that can be based on
product quality impact or risk include:
No-Impact no impact, direct or indirect, on prod-
uct quality Which Sections of a System Need to be Qualified?
Throughout my years of experience, I have often
For the purpose of this article, I will focus on the first heard industry experts discussing the need to qual-
two categories having direct and indirect impact on product ify individual components of a system versus qual-
quality. In addition, the article will focus on the Installation ifying only the critical components, for example, a
Qualification (IQ) and Operational Qualification (OQ) sec- pump within a water system. In a critical operation,
tions of the qualification process. Performance Qualifica- such as an aseptic manufacturing area whose water
tion (PQ) should be conducted exclusively on critical, direct source is a Water for Injection (WFI) system, qual-
impact systems. Test requirements should be specific to the ifying every component may make sense. However,
system and its application. a topical product manufacturer that does not have
Typical examples of critical direct impact systems would the resources to qualify every pump, assuming a di-
include a purified water system that produces processed rect impact system, must focus on the critical com-
water for formulations and a product-filler being tested for ponents.
different volumes, weights, and counts.
As discussed in the introduction, manufacturers of oral Which Pieces of Equipment within a Processing or
and topical products should focus their qualification efforts Compounding Area or on a Packaging Line Require
on critical, direct impact systems. There is no requirement Qualification?
to conduct a PQ for every system or piece of equipment in Does an OTC drug or cosmetic facility need to
the facility. Specific process or product steps, functions, and qualify storage tanks (no mixing capability) or just
parameters will be tested during the process validation for the mixing tanks and kettles? Do they need to qual-
each individual process being challenged. ify every component of a packaging line? I have
seen industry consultants require an OTC manufac-
turer qualify the line conveyors. This is neither
practical nor effective, especially for the typical
cosmetic or OTC drug manufacturer making topi-
cal products with no dosage limits.
6 I n s t i t u t e o f Va l i d a t i o n Te c h n o l o g y
Miguel Montalvo
Direct Impact Systems Risk Level I Operational requirements must be similar to new sys-
Verify the basic operational functions including the tems or equipment.
alarms that could impact product quality. Challenge para-
meter ranges and worst-cases or extremes only for critical Change Control
parameters.
The approach to change control is similar to that already
Functional Tests discussed, for example:
Test parameters at operational extreme limits Apply the same approach used for qualifying
Verify critical responses or characteristics equipment to determine requirements after change
Test minimum and maximum parameter set-point implementation.
levels without using the actual operational limits Utilize direct and indirect impact concepts to deter-
as the set points. mine the need for qualification testing and the re-
quired level for that testing.
Note: If the normal or expected parameter Make the evaluation part of the change control pro-
variation is considered, this will create a dif- cedure and documentation. Include the rationale
ferent process and the parameters values will for the decision in the procedure.
be out of limits most of the time. Ensure that the evaluation includes a determination
that the changes implemented did not create new
Controls verification more detailed hazards or risks.
Motor verification
Sequence verification (if applicable) CONCLUSION
Most system alarms verification and
reporting. Using a practical approach to determine qualification re-
quirements is essential for manufacturers in the cosmetic or
Test all alarms on the parameters and conditions that OTC drug market. Resource management is their basic
could have an impact on product quality, not necessarily all mode of operation. To remain competitive, these manufac-
of them. Need to define the list of alarms to be challenged turers must be selective in terms of the level of qualification
during the development of the specific protocol. testing and the equipment to be qualified. This article has
offered a guide to making those decisions in a procedural,
No Impact Systems documented process to provide manufacturers with a means
Systems, components, or equipment that do not fall of remaining in compliance while using their resources in
within any of the categories above will be described as hav- an effective manner.
ing no-impact or limited risk.
IQ documentation requirements for legacy systems and Mr. Miguel Montalvo is a Director of Validation Com-
equipment will be established using the same analysis as pliance for AAC Consulting Group, Inc., providing
noted above. Special considerations may be required with specialized compliance-focused consulting and
legacy systems. For example: management of validation projects for customers
Some documents may not be available. The need around the world.
for these documents must be evaluated in terms of
impact on equipment operation and maintenance. Before joining AAC in 1999, Mr. Montalvo held posi-
Documents, such as drawings and specifications,
tions of increasing responsibility in the areas of val-
idation, technical services and quality operations
may have to be developed as is or as built.
over a period of 19 years in companies such as Mil-
Data required for risk assessment may be taken
lipore Corporation, Raytheon Engineers and Con-
from historical data, such as product failures or structors, Mova Pharmaceutical Corp., Bristol-
complaints, instead of from designs. Myers Squibb, and Baxter Healthcare Corporation.
8 I n s t i t u t e o f Va l i d a t i o n Te c h n o l o g y
Miguel Montalvo
REFERENCES
Originally published in the May, 2005 issue of the Journal of Validation Technology