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INTRODUCTION
In recent years, the Food and Drug Administration
(FDA)-regulated industry has been listening to agency representatives and consultants talking about the need to implement a risk-based approach to decision-making
processes. I totally agree with the need to implement this
common-sense approach, but my question is this: Is this
actually a new approach?
Industry personnel have been considering risk in everyday decisions, but have not realized or documented these
decisions properly. I think that the key issue here is formal
documentation. In the future, the industry must focus on and
devote more time to pursuing and completing risk-related
documentation. Firms must develop procedures to adequately document risk-based decisions, estimate their criticality, and evaluate their impact. The FDA is even implementing this approach internally for its inspection plans.
Another statement with which I totally concur reads:
Risk management is nothing more than resource management. Risk management is the process of identifying the
critical areas on which each entity within the industry must
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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
SCOPE
In this article, I will describe a practical approach to applying impact and risk concepts to the processes and documentation related to facility systems and processing equipment qualifications within the cosmetic and OTC drug (topical and oral) manufacturing segments. In addition, I will
describe the procedural requirements and the documentation needed to use impact and risk concepts during the definition of the systems and equipment qualification requirements. The article is not intended to describe the Risk Assessment tools in detail, but to provide a guide for the application of these tools.
Miguel Montalvo
Within the article, I will make reference to the International Society for Pharmaceutical Engineerings (ISPE) impact concepts from their Baseline Engineering Guides
specifically to Volume #5 on Commissioning and Qualification (see Reference 2). There are three different levels of
impact: direct, indirect, and no-impact. Following are their
basic definitions:
Direct Impact System equipment or system that
will have focused and immediate impact on product quality
Indirect Impact System equipment or system expected to have incidental or secondary impact on
product quality
No-Impact no impact, direct or indirect, on product quality
For the purpose of this article, I will focus on the first
two categories having direct and indirect impact on product
quality. In addition, the article will focus on the Installation
Qualification (IQ) and Operational Qualification (OQ) sections of the qualification process. Performance Qualification (PQ) should be conducted exclusively on critical, direct
impact systems. Test requirements should be specific to the
system and its application.
Typical examples of critical direct impact systems would
include a purified water system that produces processed
water for formulations and a product-filler being tested for
different volumes, weights, and counts.
As discussed in the introduction, manufacturers of oral
and topical products should focus their qualification efforts
on critical, direct impact systems. There is no requirement
to conduct a PQ for every system or piece of equipment in
the facility. Specific process or product steps, functions, and
parameters will be tested during the process validation for
each individual process being challenged.
Miguel Montalvo
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
RECOMMENDED STRATEGIES
There are specific qualification protocol requirements
for different impact and risk-level equipment or systems.
Following are the suggested strategies for applying impact
and risk concepts during the development of qualification
protocols:
Impact Levels
Direct Impact System
Product Failure, Risk, or Hazard Level
Level I Oral or Topical Product with Dosage Limits
Installation
Include more detail as defined in the internal
policy and procedure requirements.
Refer to specific recommendations for IQ protocols below.
Operational Qualification
Consider operational functions, sequences, controls, or alarms.
Challenge Parameter Ranges, Worst-Cases, or Extremes
Use with critical parameters only.
Level II Oral or Topical Products with No Dosage Indications
Installation
Include less detail as defined in the internal policy and procedure requirements.
Refer to specific recommendations for IQ protocols below.
Operational Qualification
Consider all operational functions or sequences.
Controls exist on critical parameters.
Miguel Montalvo
Miguel Montalvo
Change Control
The approach to change control is similar to that already
discussed, for example:
Apply the same approach used for qualifying
equipment to determine requirements after change
implementation.
Utilize direct and indirect impact concepts to determine the need for qualification testing and the required level for that testing.
Make the evaluation part of the change control procedure and documentation. Include the rationale
for the decision in the procedure.
Ensure that the evaluation includes a determination
that the changes implemented did not create new
hazards or risks.
CONCLUSION
Using a practical approach to determine qualification requirements is essential for manufacturers in the cosmetic or
OTC drug market. Resource management is their basic
mode of operation. To remain competitive, these manufacturers must be selective in terms of the level of qualification
testing and the equipment to be qualified. This article has
offered a guide to making those decisions in a procedural,
documented process to provide manufacturers with a means
of remaining in compliance while using their resources in
an effective manner.
Mr. Miguel Montalvo is a Director of Validation Compliance for AAC Consulting Group, Inc., providing
specialized compliance-focused consulting and
management of validation projects for customers
around the world.
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
Before joining AAC in 1999, Mr. Montalvo held positions of increasing responsibility in the areas of validation, technical services and quality operations
over a period of 19 years in companies such as Millipore Corporation, Raytheon Engineers and Constructors, Mova Pharmaceutical Corp., BristolMyers Squibb, and Baxter Healthcare Corporation.
Miguel Montalvo
REFERENCES
1. FDA Draft Guidance on Quality Systems Approach to Pharmaceutical cGMP Regulations, September 2004.
2. ISPE Baseline Engineering Guides Volume #5, Commissioning and Qualification, 2001.
3. ISO Standards ISO-14971 on Risk Management
4. FDA webpage on Efficient Risk Management
(www.fda.gov/oc/mcclellan/strategic_risk.html) posted
8/2003 and updated 4/2004. This was included on the FDA
Strategic Action Plan developed by the agency in August
2003.
Originally published in the May, 2005 issue of the Journal of Validation Technology