CAPITULO I Análisis del sector de las frutas y hortalizas
I. 3.3.- Características comerciales y de mercado
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7.1 INTRODUCTION
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A new alternative methodology will be proposed for preparing regulated 6425
ensuring product quality or patient safety. This Baseline Guide follows 6432
the principles of ASTM Standard E2500-2007.
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Although the premise of this HVAC guide is to provide the "how" of 6435
implementing those HVAC requirements and concepts found in the baseline 6436
there is always room for improvement, but the interpretations provided 6446
Key concepts and terminology proposed for the Installation and 6450
Verification Guide are used extensively in this guide. The Baseline 6451
Guide will provide more depth regarding these concepts and terms.
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7.2 PHILOSOPHY
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The commissioning and qualification philosophy used to date 6456
incorporates Good Engineering Practices (GEP) and Impact Assessment.
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Systems and components that were designated as Direct Impact were 6458
subject to qualification, in addition to commissioning. The difficulty 6459
encountered in this process is that some companies found it difficult 6460
to leverage commissioning activities and documentation into 6461
qualification, so they re-commissioned a system to gather qualification 6462
documents. Some of the compliance-related activities included general 6463
engineering-focused activities that added little or no compliance value 6464
(such as qualifying fan speeds or prefilters).
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The new methodology is based on:
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Use of risk assessments (instead of impact assessments) to determine 6471
the scope and extent of required verification in the overall Risk 6472
Management Process, which is related to patient safety 6473
Notion of Design Space 6474
Focusing on practices that lead to achieving fitness for purpose.
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7.3 PRINCIPLES
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Key principles that provide the basis for developing engineering 6479
requirements are:
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The assessment and designation of criticality should be primarily 6482
based on impact on the safety and efficacy of the drug product to 6483
the patient 6484
6485
Critical Quality Attributes (CQAs) should drive the focus of the 6486
risk assessment along with Critical Process Parameters (CPPs) 6487
6488
Risk assessment shall be performed in the "design space", the 6489
intersection of CQAs and CPPs, and is subject to regulatory 6490
assessment and approval.
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The Installation and Verification process shall have value added 6493
activities and shall remove those activities that are wasteful and 6494
non-value adding.
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Verification practices performed solely for regulatory compliance 6497
should be avoided. 2 6498
6499
7.3.1 Good Engineering Practice 6500
6501
Good Engineering Practice (GEP) is the practice under which all 6502
engineering activities and documentation are created. It applies to all 6503
facilities, not just pharmaceutical facilities. GEP encompasses the 6504
following:
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Design and installation that takes full account of cGMP, safety, 6507
health, environmental, ergonomic, operational, maintenance, 6508
recognized industry guidance, and statutory requirements.
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Professional and competent project management, engineering design, 6511
procurement, construction, installation and commissioning 6512
demonstrating functionality per design specifications.
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Appropriate documentation, including design concepts, design 6515
schematic drawings, as-installed drawings, test records, maintenance 6516
and operations manuals, statutory inspection certificates, etc.
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Well planned commissioning activities and documentation following sound 6519
Engineering Principles and Good Engineering Practices make a 6520
significant contribution in preparing for and achieving first time 6521
success to meet installation and verification requirements.
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2 If a practice adds to the assurance that the equipment or system will work as intended then that practice should be performed whether or not the system is part of GMP manufacturing operations. If it does not, then that practice should not be performed unless specifically required for compliance.
7.3.2 GMP 6524
6525
Sustainability and Commissioning/Verification 6526
6527
TEXT NEEDED 6528
6529
7.4 REGULATORY EXPECTATIONS
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TEXT NEEDED 6532
6533
US – This approach is recognized by the FDA as ONE method of verifying 6534
fitness of the HVAC system for production. Activities in this approach 6535
follow the principles in ASTM E2500.
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EU – unknown at this time whether EU regulators will accept less 6538
voluminous Qualification packages.
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Other - ? 6541
6542
Regulatory expectations are covered by the appropriate ISPE Facility 6543
Baseline Guide. As these expectations sometimes change, this guide 6544
defers to the Baseline Guides.
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7.5 KEY CONCEPTS OF VERIFICATION
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The verification process for HVAC Systems is a subset of the 6549
verification process for the manufacturing system. These key concepts 6550
have been driven by the FDA Initiative Pharmaceutical cGMP‘s for the 6551
21s Century – A Risk Based Approach, and by ICH Q9 Quality Risk 6552
Management. The overall direction is a shift toward the safety of the 6553
07 to the installation and verification of HVAC Systems.
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The goal of this approach is to improve patient safety while 6559
controlling costs and reducing non-value adding effort.
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It should be noted that these Key Concepts focus on patient safety and 6562
product quality (GMP). The verification of the specification and 6563
design as it impact worker safety, health, environmental and other non-6564
GMP concerns should also be considered.
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7.5.1 Risk-based and Science-based Approach 6567
6568
The level of risk to product quality should be based on scientific 6569
knowledge that leads to protection of the patient. The level of effort 6570
risk-based decision to insure that manufacturing systems are designed 6574
and verified to be fit for their intended use.
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Considerations include Critical Quality Attributes (CQAs), Critical 6577
Process Parameters (CPPs), process control strategy and prior 6578
production experience.
7.5.2 Critical Aspects of Manufacturing Systems 6585
6586
Critical Aspects of Manufacturing Systems are typically functions, 6587
features, abilities, and performance characteristics necessary for the 6588
manufacturing process and systems to ensure consistent product quality 6589
and patient safety.‖ HVAC systems may affect the manufacturing system 6590
and the critical aspects. Verification activities should focus on the 6591
critical aspects of the Manufacturing system and HVAC subsystem‘s 6592
effect.
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7.5.3 Quality by Design 6595
only phase activity.
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7.5.4 Good Engineering Practice 6601
6602
Good Engineering Practice a set of established engineering methods and 6603
standards that are applied throughout the life cycle to deliver 6604
appropriate and effective solutions. For HVAC systems GMP 6605
requirements, code requirements including sustainability requirements 6606
and energy efficiency, safety, health environmental, ergonomic 6607
operational, and maintenance must be address. Preceding chapters 6608
discuss how to implement Good Engineering Practice for HVAC systems.
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7.5.5 Subject Matter Experts 6611
6612
Subject Matter Experts have specific expertise and responsibility in a 6613
particular area or field . For HVAC Systems this could include the 6614
HVAC Engineer, quality unit, automation, or operations.
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7.5.6 Use of Vendor Documentation 6617
equipment or system.
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7.5.7 Continuous Improvement 6625
6626
Continuous improvement can happen as information is gained from 6627
operations. Improvements can be based on periodic reviews and 6628
evaluation, operational data and root-cause analysis of failures. For 6629
HVAC systems energy optimization is typically reviewed. Such 6630
improvement should be encouraged, although current Change Management 6631
programs often discourage change for any reason.
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7.6 DESIGN, SPECIFICATION, VERIFICATION, AND ACCEPTANCE
they relate to the overall specification, design and verification 6638
process for the manufacturing system as well as HVAC subsystem. For a 6639
7.6.1 Requirements Definition 6643
6644
Product Knowledge, Process Knowledge, Regulatory Requirements and 6645
Company Quality requirements all must be considered when determining 6646
the requirements for the manufacturing systems and HVAC system. The 6647
requirements definition is driven by patient safety. See chapter 3 for 6648
more detail.
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7.6.2 Specification and Design 6651
7.6.3 Verification 6656
Commissioning Plan or Verification Plan for Facility and Utility 6661
Systems will include the HVAC system and controls.
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The HVAC engineer's role in verification will be different from in the 6664
impact assessment process. Under the ISPE Commissioning &
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Qualification Baseline Guide, systems were determined to be either 6666
direct impact or indirect impact. The HVAC engineer was part of a team 6667
that supported, developed, and executed commissioning and qualification 6668
qualification for direct impact systems by leveraging documents and 6673
procedures to streamline the process and reduce redundant testing and 6674
non-value added activities.
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making such a change.
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not if this is a direct or indirect impact system, but rather what are 6686
the elements of this system that are critical to product quality and 6687
patient safety, and how can we manage those risks appropriately to 6688
maintain or improve our overall product quality?
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The interdisciplinary expert team forms the foundation for developing a 6691
risk management plan. Team members decide on methodologies to 6692
determine acceptable levels of risk and appropriate tools to evaluate 6693
risk (e.g. FMEA) after identifying the User Requirements. User 6694
Requirements should identify the Critical Process Parameters (CPP), 6695
Critical Quality Attributes (CQA) and other critical aspects related to 6696
product quality and patient safety.
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Once the critical aspects (CPP, CQA, etc.) have been identified by the 6699
interdisciplinary team and documented, the quality unit then approves 6700
this document as the basis for the Verification Plan that will be 6701
developed. Furthermore, engineers need to know what type of tests the 6702
quality unit will expect to be performed after the verification process 6703
is complete in order to prepare systems to pass these tests.
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Verification, similar to ―commissioning and qualification (for direct 6706
impact systems)‖, is one process that covers the activities, testing, 6707
and documentation required to evaluate systems, equipment, and 6708
tests to be performed are developed by the Subject Matter Expert (SME).
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For example, the HVAC SME would design a verification plan that would 6713
verify the acceptance criteria that meets the critical aspects (CQA, 6714
CPP …) within the framework of the risk management plan.
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For an overview of the verification process, refer to figure 7.1:
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7.6.4 Commissioning & Qualification process – SEE APPENDIX 6719
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7.6.5 Acceptance and Release 6721
6722
The acceptance and release phase confirms that the manufacturing system 6723
and support HVAC system are fit for their intended use. This is the 6724
last check before initial operation.
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7.7 SUPPORTING PROCESSES
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The activities described here can be part of the Specification, Design 6729
and Verification (SDV) Process. They occur throughout the SDV process.
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7.7.1 Quality Risk Management (QRM) 6732
process for the manufacturer. The Risk Assessment for the HVAC system 6736
should be addressed in the overall Risk Assessment activity..
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7.7.2 Design Review 6739
6740
Design reviews are planned systematic reviews of specifications, 6741
design, design development and continuous improvement changes performed 6742
throughout the life cycle of the manufacturing system. For HVAC 6743
systems in the design phase, reviews typically occur at the basis of 6744
design (BOD), schematic design, design development and construction 6745
document phases. HVAC equipment specifications are often not available 6746
until the construction document phase and their review is critical to 6747
system quality.
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7.7.3 Change Management 6750
6751
Change Management should be implemented on changes that affect critical 6752
aspects of the manufacturing system, both before and after acceptance.
6753
After acceptance, changes that affect GMP critical parameters need to 6754
be approved by the Quality unit prior to implementation. With 6755
continuous improvement as a goal of the FDA initiative, it is expected 6756
that systems that have been verified and accepted for intended use will 6757
be modified to achieve improved patient safety or reduce operating 6758
costs as opportunities arise during the manufacturing system‘s life 6759
cycle.
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