Necessity of the verification of pharmaceutical engineering

Many pharmaceutical companies increasingly feel the difficulty of the new version of GMP certification. Among them, a considerable number of small and medium-sized pharmaceutical companies have fewer production lines and lack of risk prediction on the change of laws and regulations. There is no institutional regulation on their plant design and regular renovation and upgrading, which necessitates long-term transformation tasks before the new GMP deadline. However, discontinued production faces the threat of losing market without stopping production.

GMP, the Chinese meaning is "production quality management practices" or "good practices," "good manufacturing standards." In a nutshell, GMP requires manufacturers of pharmaceuticals and foodstuffs to have good production facilities, reasonable production processes, sound quality management and strict testing systems to ensure that the quality of the final product, including food safety and hygiene, meets regulatory requirements.

Many pharmaceutical companies increasingly feel the difficulty of the new version of GMP certification. Among them, a considerable number of small and medium-sized pharmaceutical companies have fewer production lines and lack of risk prediction on the change of laws and regulations. There is no institutional regulation on their plant design and regular renovation and upgrading, which necessitates long-term transformation tasks before the new GMP deadline. However, discontinued production faces the threat of losing market without stopping production.

First, the verification activities in the role of pharmaceutical engineering

● To ensure the integrity of the pharmaceutical engineering quality derivation process

Since verification is the process of derivation of quality, then in order to ensure the integrity of the derivation process, verifying the professional participation in the whole process of the project is an inevitable choice. This is a qualitative requirement.

This is also true. Since 2010, many foreign-funded enterprises have clearly pointed out that when looking for a construction contractor, they need to verify the full participation of experts. It is interesting to note that more than 50% of these inquiry companies are not pharmaceutical projects or even life science projects. According to the pharmaceutical industry, these projects are not validated.

Systematic to ensure the smooth progress of pharmaceutical engineering

As a process of deriving quality, verification is done through a series of activities to ensure its effectiveness. This is a quantitative requirement.

As a result, many companies request engineering contractors to present verification management systems and successful project cases after they have been asked for verification. Verify execution has become an indicator to judge the project contractor's ability.

● Pharmaceutical engineering and end-user compliance an important part of convergence

Validation is a proactive activity for the project itself; for a pharmaceutical project, not only to meet the validation needs of the project itself, but also to validate the requirements described in the pharmaceutical industry regulations. In other words, at this stage, the contents of the validation of pharmaceutical engineering may be more stringent.

Now we can understand that: If the project management company and you talk about verification, it does not necessarily mean that the GMP verification; GMP consulting firm and you to verify that it must not be verified in the engineering sense; only focus on Pharmaceutical engineering project management company and you talk about the verification, it may be that we are concerned about the validation of the pharmaceutical engineering. Unfortunately, after experiencing the industry turmoil in 2011-2013, no engineering management company focused on pharmaceutical engineering validation exists in China.

Second, verify the management system and quality management system

● Verify the relationship between the management system and the quality management system

For the engineering management company, the quality management system is the company's ISO system, there must be; verification management system is a separate set of working documents, not necessarily an integral part of the quality management system.

● project verification management system and project quality management system

Project quality management system and project verification management system are developed by engineering contractors and pharmaceutical companies and act on the designated project management system. Both can be part of a project's implementation plan.

● project verification management system

For the pharmaceutical project, the project verification management system not only meets the requirements of project verification, but also meets the GMP requirements of pharmaceutical companies for all phases of pharmaceutical engineering. There are two elements here, one based on the project itself and the other based on a specific target industry.

Therefore, in the construction of pharmaceutical engineering verification management system, we should pay attention to include the following aspects:

➤ Engineering Industry Verification Requirements.

➤ Validation Requirements for Pharmaceutical Industry.

➤ Verification Requirements for Device Vendors.

It is important to point out that the construction of the project verification management system is the result of discussions among various stakeholders in the project. Here we must pay attention to identify a misunderstanding: equipment suppliers or contractors to provide a one-sided verification management system is limited and can not be directly used as a verification project management system for the use of pharmaceutical engineering.

Verification is a quality-derived activity. Equipment suppliers also have to do their own quality to derive their own activities. In other words, device vendor verification is not a true subset of pharmaceutical engineering validation.

Strictly speaking, the verification of equipment suppliers also covers the complete life cycle of their products. In this sense, the supplier verification required by our pharmaceutical engineering verification should be the intersection of complete supplier verification and verification of pharmaceutical engineering!

Steam Sterilizer Validation Requirements Per The New Standard ISO 17665-1:2006

For decades, steam sterilization (autoclaving) has been an integral part in the manufacturing, cleanroom, and laboratory processes for the medical device, pharmaceutical, biologics, and human tissue/HCTP industries. It has been a common industry practice to validate steam sterilizers using the published guideline ISO 11134 Sterilization of health care products — Requirements for validation and routine control - Industrial moist heat sterilization,1 issued in 1994. In late 2006, AAMI released the document intended to supersede 11134, with ANSI/AAMI/ISO 17665-1:2006 Sterilization of health care products — Moist heat — Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices.2 While other steam sterilizer guidance documents do exist,3,4 it is anticipated that the new 17665 standard will be recognized by the FDA and will be commonly employed to validate autoclave processes. The good news to manufacturers or other users of these guidelines is that many of the current validation practices are the same in the new document. This article will outline the basic requirements for steam sterilizer validation via the halfcycle overkill method, and list some of the differences between the two documents.

REQUIREMENTS PRIOR TO VALIDATION
The 17665 document makes it clear in numerous locations that the user’s quality system must adhere to ISO 13485:2003 Medical devices — Quality management system — Requirements for regulatory purposes.5So if a user wishes to claim full compliance with the new 17665 steam standard, then their quality system must also be in compliance with ISO 13485, including items such as preventive/periodic maintenance and regular calibration for the sterilizer, documentation, change control, purchasing, etc. When compared with the previous steam document, the new 17665 also has more information on product and process characterization, sterilizing agent characterization, installation qualification/IQ, and operational qualification/OQ. The new document also states more clearly that a fully compliant validation is not just a series of successful halfcycles,but is the full complement of successful IQ, OQ, and PQ.

Sterilization agent characterization will be simple for most users — moist heat/steam at 121 or 132 °C, and cycle selection (gravity, prevacuum, etc.). Process and equipment characterization means defining and documenting items like the sterilizer cycle parameters, products (or product families) to be sterilized, load configurations and limits, placement of biological indicators or chemical indicators (BIs/CIs), process tolerances, and equipment identification. Much of this type of information would be recorded in well-written validation protocols or validation final reports. Biological indicators often use spores of the bacterial species Geobacillus stearothermophilus at a titer of greater than 106per BI, although other species or titers are sometimes used.

The new 17665 document also has more information on IQ and OQ. It defines IQ as “obtaining and documenting evidence that equipment has been provided and installed in accordance with its specification.” Autoclave installations commonly document items such as the sterilizer identification numbers, location, line voltage and amperage, water supply piping and pressure limits, steam line requirements, filtration, chamber size, structure and support, piping materials, software certification, manuals, drawings and documentation, and calibrations (temperature, pressure, and timer). The sterilizer must be installed in such a manner to facilitate any necessary maintenance, repair, adjustment, cleaning,and calibration.

OQ is defined as “obtaining and documenting evidence that the installed equipment operates within predetermined limits when used in accordance with its operational procedures.” Autoclave OQs commonly test or verify items such as cycle operation and programming instructions, safety and alarm testing,error reporting, empty chamber temperature profiling and chamber temperature limits/specifications, air removal testing, leak testing, temperature control anomalies, full cycle full-load temperature profiles (if proposed fullcycle exposure time is known), and determination of any hot or cold spots withinthe chamber.

The product definition and process definition sections of the new document list things such as product specifications, product families, packaging, re-sterilizationissues, package moisture, stability and potency of container products, re-usablecontainer systems, process challenge devices/PCDs, sterility assurance level/SAL,BIs and CIs, and bioburden determination if necessary. PCDs are described asproducts or items that provide a known resistance to the sterilization process.They are commercially available or may also be created from the user’sproduct line by inserting spore strips, spore dots, inoculated threads, etc.into items or locations that are determined to be the most-difficult-to-sterilizeproduct or location in the load.

There are many other activities or decisions to be made prior to or during the IQ/OQ, that are not necessarily detailed in either standard. Items such as:

• Obtaining calibrated temperature recording devices or thermocouples
• Ordering supplies such as BIs, CIs, Bowie-Dick test packs, packaging materials, etc. and noting if adequate laboratory facilities are available
• Determining worst-case validation load and worst-case test product or PCD. The protocol or final report should contain a written rationale describing how the loads and product(s) were selected
• Selecting cycle type: 121 or 132 °C, gravity or prevacuum cycle, etc.; and determining if drying time needs to be qualified
• Is product bioburden testing necessary?
• Is product resterilization to be allowed and what are the requirements for resterilization?
• Is product stability or shelf life testing necessary for the user’s products?
• Does packaging testing or packaging validation need to be included with the protocol?

VALIDATION – PERFORMANCE QUALIFICATION 
AAMI TIR #13 states “Sterilization process validation is a documented procedure for obtaining, recording, and interpreting the results required to establish that a process will consistently yield product complying with its predetermined specifications.” For the purposes of this article, the primary specification will be sterility. The performance qualification/PQ or microbiological qualification is a series of tests that establishes that the installed and properly operating sterilizer will process the users desired chamber loads to achieve the specified sterility assurance level/SAL. It must be remembered that the load is part of the validation — that is, if the user makes significant changes to the load at any point in the future — then re-validation may be necessary. The previous ISO 11134 document gave relatively little guidance information and few specifications for conducting the test cycles necessary to qualify the user’s proposed fullcycle exposure time(s). The new 17665 steam document varies little from the previous standard in respect to the minimal PQ information that is provided. The 17665 describes bioburden validation methods and the more commonly used halfcycle “overkill” method. It should be noted that at the time this article was prepared, the proposed guidance document that is to accompany ISO 17665-1 was not yet available. This guidance document may provide more advice on microbiological qualification issues (ISO 17665-2 Sterilization of health care products — Moist heat — Part 2: Guidance on the application of ISO 17665-1). For this article, the general requirements for an overkill cycle PQ will be reviewed.

While many activities are required to complete the PQ, the primary goal for the commonly employed overkill validation is this: the user needs to complete three consecutive successful halfcycles in order to qualify their proposed fullcycle exposure for routine processing of sterilization loads. In our case, successful means all BIs are killed (no growth upon incubation) for the three consecutive halfcycles. If, for example, there was no BI growth for the three test cycles at ten minutes exposure at 121 °C, then a 20-minute exposure at the same temperature would be adequate for routine daily processing, assuming all other aspects or requirements of the IQ/OQ/PQ are successful, documented, reviewed, and approved.

But a description of the PQ needs much more detail than this. Validation protocols vary in format from company to company, but most will capture similar information for the final report. An example of validation protocol and final report sections would be:

• Title page with approval signatures
• Purpose, background information, or general goal(s) of validation
• Scope with more specifics about methods, cycles, facility, SAL, products and load, exclusions, etc.
• References with published standards and company SOPs
• Equipment, supplies, validation loads, BIs, etc.
• Rationale for selection of products, load, cycles, PCDs, etc.
• Procedure or methods (more details on this below)
• Acceptance criteria which list the pass/fail requirements
• Deviation report which lists any unexpected results, with potential effects on the validation, along with accept/reject rationale
• Results and conclusions which assign a pass/fail decision to each acceptance criteria, summarize study, and include any requirements for revalidation
• Attachment which lists any data sheets, diagrams, certificates, temperature records, etc., for inclusion with final report
• Approvals section for final report.

To conduct the halfcycles, the user assembles the worst-case validation test load, temperature loggers, BIs/PCDs, and CIs if necessary. The temperature loggers and BIs are seeded throughout the load to represent various chamber locations, keeping in mind any cold spots or previously determined most-difficult-to-sterilize locations. For small chambers, as few as five or six BIs and temperature loggers may be needed. Ten is a common sample size for many chambers. Large, multi-pallet-sized chambers may require many more samples per run. The sterilizer is programmed for one-half of the proposed full-cycle exposure time. Upon completion of the test cycle, the BIs are immediately removed and incubated, and the test load must be allowed to return to normal temperature prior to starting another test cycle. Temperature recorder data is downloaded and printed immediately to determine if any unusual temperature conditions existed. Information is entered on thedata sheets (data sheets that would have been one of the attachments to the written protocol), and all temperature records and data sheets are retained for the final report. BIs are checked regularly throughout the incubation period, and include positive control (unprocessed) BIs which must show growth. As stated before, all processed BIs must show no growth in order for the validation runsto be considered successful.

Final reports should contain: 1) all sterilizer run data or recorder charts, signed and reviewed; 2) all temperature recorder data, signed and reviewed; 3)all data sheets with BI, CI, or any other test results, reviewed and signed;4) any deviations recorded and investigated, with final disposition; 5) results,conclusions, and discussion; 6) calibration documents for any measuring instrumentsused during the study; 7) the approved full-cycle parameters and acceptable placementlocations for BIs for normal processing; and 8) manufacturers’ certificatesof analysis for any items such as BIs, growth media, growth promotion test cultures,etc. Including digital photographs of sterilizer, load, PCD, etc. can be quitehelpful for an auditor who may be reviewing the report at a later date. The completedfinal report packet must then be routed for review and signed for approval.

POST-VALIDATION
There are still issues to be addressed when all activities seem to have been completed. The sterilizer must be added to a regular and documented calibration program. The sterilizer must be included in a regular and documented periodic/preventive maintenance program. And the sterilizer must be added to the validation schedule for its annual requalification. The user needs to verify that all personnel that will be using the autoclave are trained using applicable operation and safety SOPs. Untrained staff should not be allowed to run the sterilizer. Approved products, loads, cycles, and load limit information must be readilyavailable to all operators. SOPs for daily processing must list all requirements for data that is to be reviewed and retained from the sterilizer runs, with logbook, filing system, or archive for run records. SOPs must also address items such as 1) segregation of processed and non-processed product, 2) storage requirements for processed products if necessary, 3) notification of management or maintenance if sterilizer malfunctions or if recorder chart lists any errors, cautions, or warnings, 4) immediate notification of management for BI test failure, including investigation and product quarantine procedure as appropriate, and 5) resterilization requirements if resteril-ization isto be allowed.

In summary, there seem to be no drastic or revolutionary changes in making the transition from ISO 11134 to ISO 17665. The new 17665 steam document provides more information and more guidance in some areas, while leaving other areas (such as PQ) relatively unchanged. While users would be advised to obtain the 17665-2 guidance document when it becomes available, it is anticipated that manufacturers will not find any great difficulties in applying the new standard.

References

1. ISO 11134:1994. Sterilization of health care products — Requirements for validation and routine control — Industrial moist heat sterilization.
2. ANSI/AAMI/ISO 17665-1:2006. Sterilization of health care products — Moist heat — Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices.
3. AAMI TIR No. 13-1997. Principles of Industrial Moist Heat Sterilization.
4. PDA Technical Report #1. Validation of Steam Sterilization Cycles. Parenteral Drug Association.
5. ISO 13485:2003. Medical devices — Quality management systems — Requirements for regulatory purposes.

Mark Dott performs consulting work in the areas of sterilization, sterilizer validation, and microbiology test methods. He can be reached at Mark Dott, LLC, Castle Rock, CO 80104; 303-437-4946, dottmj@mho.com, www.MarkDottLLC.com.

Why Validate?

Similar to what the FDA has imposed in the pharmaceutical, biopharmaceutical and medical equipment industry, the food production sectors must validate the production processes of high-risk foods to ensure that all systems have a consistently high level of assurance to produce a product that consistently meets the pre-designed specifications. This gives a company a control system that is consistent and reproducible.  Furthermore, a validated process is credible and stable, because the acceptance criteria are already specified in the qualification phases of the validation.

If the specifications of the system, how it is designed and how it works are known, it will be possible to maximize the performance of that system.  If the validation is carried out correctly and with the right objectives, it can be a process with added value for the company.

Facility Monitoring Systems Validation: A Practical Approach

Meanwhile, most Pharmaceutical professionals have a detailed understanding of the process's process, and understands little of the process of validating computerized systems.

The problem is, of course, that microprocessors are now being built around the entire pharmacy.  These include stock control, integrated production, environmental monitoring, laboratory analysis, vision testing systems, and even recorders and temperature controllers.  To ensure the integrity of the process, each of these devices must be properly checked as part of a larger authentication process.

Simply having the concept of computers and software systems is not enough, it's not only necessary to fully understand the process, but also the certified equipment.  It can be difficult because those who are best aware of the equipment are the manufacturers, but often they can learn more or less about ratification.

This article applies only to one of the important features of computer systems validation. Lending System Documentation  (FMS).

FMSs are commonly used for purity and adjacent areas.  Such systems can not be used for the classification of space or objects.  they carry out only monitoring functions that indicate that the environment in the controlled area has been maintained within the defined limits.  However, the FDA and other regulatory authorities recognize that the recycling period for FMS users may be prolonged (see ISO 14644-2).

FMS usually includes several monitoring devices: temperature, humidity and pressure sensors or switches, as well as speed sensors and particle counters.  It can also include digital equipment for monitoring vacuum pumps or vehicle driving states and digital output signals / signal indicators, such as lights or sirens and other control functions.

Documentation:

The most important document for the proposed system is  User Requirement Specification (URS).  Without this document, it is not possible to validate the system.  This is a definite surprise,  but ratification is determined by the process of generating no more than a documented evidence to ensure that the system consistently performs its function.

URS mentions the required system functions.  It should not be long, but it should indicate that the system should perform the functions.  Despite his name, there is no need for URS to emerge.  the provider may issue a document, but the URS must be authorized by the user.  Its purpose is to ensure that both the user and the provider understand what is required.  The document must have the  required shots  ,  like-places  , and  would like to make it better  .  The customer must provide all the  mandatory reserves  , but do not necessarily  want to know some  of the  things and good things  .

All other URS authentication papers and stages follow.  This progress is usually displayed  on this article described  the practical  validity of the model (V- model) form .  These documents and processes are presented as  Life Cycle Documents.

After URS, the next step causes the provider to have a  functional feature (FS).  This document, which should address all users,  should have the desire to have it and  it will be best  to set up before installing.  If certain requirements can not be met, as inevitably would be the case, the discrepancies should be listed within the FS.  Very often the requirement may be fulfilled in another way.  Sometimes the demand is not even important.  The FS should include a cross-reference matrix so that the user can easily see how the supplier offers each claim.

At this stage, the user must request from the provider to produce a  Quality Plan (QP)  or  Master Validation Plan (MVP)  , where the provider determines how the program will control who will be responsible for each stage of the project and on time scale at each project stage.

The system has been fully clarified and agreed upon in the FS, the design of the system should be defined  within the framework of the General Design Specification (DS)  .  This clarification should be a high-level document that clearly outlines what materials are required and how mechanical and programmatic points should be connected to meet the functional adjustment requirements.

Design Qualification (DQ) is  associated with URS, FS, and DS.  It is necessary to verify that all the items listed in the previous document are addressed (not  addressed , but addressed  ).  DQ prevents the claim.

Next  Module Specifications (MS)  .  The "module" can be a control panel or program.  It does not matter.  If something needs to be built or programmed, the module requirements must be clearly defined.

Test stage:

The ultimate operation of the first part of the V-model is actually building panels, ordering particle counters and related equipment or equipment, and then writing and / or configuring the software.  But since this V model shows, this is only half of the program.  When all the equipment has been built or shipped on a provider's site and its written and configured programs, the system must be enabled and tested to ensure that all the work is done.

Module testing should be developed against the module specifications to ensure that each module functions.  In the case of a console, it is important to ask whether all the equipment is installed, whether it is properly wired and whether it meets all the relevant criteria.

By software, it is wider for conventional modular features than the user's requirements.  This allows modules to be restarted in other projects.  But it is important to be sure that the module, as mentioned, acts as declared.  Again, the clarification of the module is used to process a number of tests that confirm that all functions have been completed and acted as specified.  This set of tests should include software stress testing to ensure that normal error conditions are correct.

After the modular test system should be consolidated, and then  used for the application of the completed system  tests in another package (  Software Quality, SQ  ), to ensure that it functions as a DS- in detail within.  Some companies do this on the site, but if there is one problem, they will bring the added costs of staff to the site, and usually design engineers are out of place.  Simulators should be used when the system installation site is difficult or impossible.

Users can note that they want to make a  factory admission exam (FAT)  .  This is very common with the delivery of cars, but not least with the FMS.  The purpose of FAT is to see how the system operates before it can be used to reach it (this is also usually the payment stage).  The best way to perform FAT is to use the System  Deployment Qualification (IQ)  ,  Operating Qualification (OQ)  and  Manufacturing Qualification (PQ)  documents and reference the tests that are used simulators have been applied as applicable or the test is feasible. Again, if there are any trial failures, it is much simpler and more expensive to solve the problems on the vendor's website than on the user.

Or, after SQ or FAT, the system is installed, installed, and delivered.  After handing over the system, I strongly recommend that the user be prepared before and after the final validation tests (IQ / OQ / PQ).  There are two factors for that. Inevitably small differences will be between what is required by the URS and the operators actually use the system.  Training before IQ / OQ / PQ allows for these small differences to change under control, while other documents are revised.  Additionally, within the IQ framework, a test should be made that users have been trained.

From now on, any changes to the system should be taken very seriously.  Change control should be applied.  (Actually, change control should be applied before this phase as any change may have an impact on correction documents and previous attempts, in the ultimate case, one seemingly innocent change can actually lead to failure because it can be "erroneous" is presented):

Supply modular tests and SQ tests can be quite informal.  By that I mean that the tests should not be encouraging.  This allows engineers to really try the system without spending too much time producing test documents.  The purpose of the test, however, must be clear and must be based on evidence that the test has been performed.  Tests during IQ / OQ / PQ should be very encouraging for the user to experiment.  Test evidence should be more than a check box label. Physical test evidence (print, screenshots, photos, etc.) should be provided. This is mainly a test evidence that will be submitted to the MCA or the FDA Inspector showing that the function is carried out as needed.

The  installation qualification (IQ) during the test  may be different.  IQ tests should confirm that all the products listed in the functional specification are shipped and are the correct type.  FS can declare that 0-100 Pa differential pressure switches should be used with accuracy of 1%.  Is it there

The IQ test should test and confirm that:

• All the installed sites are presented or better.
• All support systems are installed (manuals, technical manuals, system diagrams, etc.).
• All the tools have been checked and the verification is still in effect.
• All software systems (CDs) are available and have been properly filed.
• At this point, the footprint (system files, dates, and dimensions) has been taken.

The system must be able to be re-certified later.  To ensure IQ testing, all inputs / outputs of the data collection unit are operational and must be implemented to ensure that all switches, lights, switches and their functions are performed.  These tests can be considered as practical tests.  some companies include such tests as  Operational Qualification (OQ) test documentation.  When it has been documented that the system has been supplied within FS, OQ may begin.  OQ's goal is to verify that the system is functioning (as described in FS). Experiments must show that all the products listed in FS have been tested, but tests should be more than that, especially for FMS, or in any case with any data collection system.  There should be clear tests that show the correct collection of data and these manipulations are used correctly, and these data are stored correctly and can be correct.

Tests to verify the size of the colors and fonts on the systems are accurate, but they add little to ensure that.

The final part of the test is  performance test (PQ)  .  Usually, PQ tests are designed to ensure that the machine operates at the right rates, with the user product.  However, object monitoring systems are not applied, and in many cases PQ is not implemented.  In areas where previously used enterprise methods were controlled by the object (with moving particle calculators, for example, and other tools), the comparison of the mobile particle counters and the FMS particle counters is performed.  This can often result in test failures due to differences in particle optics, electronics, and test methods. When this happens, I strongly advise that the particle counters products are contacted for guidance.

Other documents should also be set up for complete authentication.  The  baseline is the Project Completion Report (PCR)  or the  Ratification Exam Report (VRR)  .  The Project Validation Summary, VRR must submit all the documentation that has been generated with the test results and must include a clear statement for system exploitation.

Vendor audits  also apply to users.  They should be performed prior to placing the order in order to ensure that the supplier is a good quality system and can provide the necessary system.

21 CFR, Part 11 Regulation

21 CFR, FDA Regulation 11 deals with electronic signatures and electronic records.  Most environmental monitoring software systems do not use electronic signatures to confirm the batch release information.  However, all monitoring software systems have electronic data, so the regulations apply.  In general, object monitoring systems are closed systems that are accessible by system and system data tracking.  In this case, although the provision of electronic signatures is not applicable, subparagraph B is applicable to this paragraph 11.10.

Part B, paragraph 11.10, in particular, specifies the following:

• The system must be validated.
• The system should be able to create accurate, complete data copies.
• Data records should be protected.
• System access must be limited.
• Audit trails should be used for all data.
• If possible, the operating system protection methods should be used.
• Authorization checks should be applied.
• Data entry / assembly checking should be applied.
• Users should be trained.
• Standard operating procedures (SOPs) should be on-site.
• Documents should be monitored.
• Change control should be applied.

Tests should be included within IQ and OQ to find out that the system actually performs the above requirements.  Many should already be part of any trial, but some are not the supplier's scope.

Here are some simple ways to make the process easier and ensure that the system passes validation.

• Be sure that all switches, particle counters and other devices are suitable for the purpose and have valid validation certificates.
• Do not use complex data collection devices, such as programmable logic controllers (PLCs) if they are not required.  If PLC is used then it will have a program and additional validation will be required.
• When designing the system, consider how to check things and how to make documented evidence.
• Think of the requirements of Part C of 21 CFR and how they will be fulfilled.
• Use qualified people and reputable providers.
• Follow the steps outlined in this V-model scheme.

Principles of Cleanroom Validation

A clean room is a modular environment in which the following environmental factors are controlled; temperature, particles in the air, microbes, relative humidity, differential pressure and air flow.In Cleanroom validation is performed for various reasons.To ensure that the design of the facility is adapted to the intended use; ensure that the installation, equipment and the environment are the specifications of requirements of users (URS); ensure that the installation, equipment and the environment meet the defined regulatory requirements; make sure that the installation, equipment and its environment work together as a system that meets defined standards.Cleanrooms are validated and certified according to ISO 14644-1 class.Each class of ISO14544-1 has its unique requirements that need to be made so that a facility be closed within the specified classification.LIFE CYCLE of VALIDATION the validation of a new clean room air conditioning room follows a specified life cycle.The life cycle includes five phases which each performs specific tasks to control the variation in the modular environment.Validation in Cleanroom work is done in five phases.It starts with the control of design phase and ends with the control and the control.Changes to the equipment and control factors after the validation of the cleanroom justify the revalidation of the cleanroom.

PHASE one: QUALIFICATION of the design the cleanroom validation starts with the design qualification (DQ).The purpose of this phase is to prove by objective evidence that the design is suitable for the use for which it is intended.The qualification of design is an exercise in check against the requirements defined in the acceptance of your DQ Protocol criteria.The Protocol should address the following points: user (URS) Documents of the supplier requirements Specifications and specifications facilities buy online design Documentation (FAT) factory acceptance Tests as construction drawings data sheets out of the qualification of design phase is a phase report and a list of standard documentation file (SDL), which documents the following: design Conditions of auction purchase requirements and order documentation list of the documents provided by the supplier as construction drawings, lists of lists of inspection acceptance Tests components factory approval of the qualification of design phase, DQ is a prerequisite for the initiation of the installation qualification phase, QI

PHASE 2: QUALIFICATION for the INSTALLATION the objective of this phase of installation (QI) qualification is confirmed by the audit equipment, as installed, confirm the requirements of the user and design requirements.The audit focuses on the following which should be requested in your QI Protocol: calibration HVAC check loop P & ID data review of the integrity test of the filter HEPA State of calibration of critical equipment Tests acceptance of installation qualification Tests (SAT) site Documentation piping and welding audit of the utility of the system's standard operating Procedures and work instructions the result of this phase should be an IQ report dealing with all of the above, and an SDL file that documents the following: changes of project Tests of QI made calibration Documents supplied by the supplier certificate of equipment installation acceptance Tests goodwill of site (SAT) list of consumables list spare parts list of the documents operational environmental review report and teaching the approval of QI is a prerequisite at the beginning of the phase of operational qualification (OQ).


PHASE 3: QUALIFICATION of the operation the objective of this phase of operational qualification (OQ) is to show by objective evidence that the white room works in accordance with the design requirements and the requirements defined by the user and it works constantly in a defined range of conditions.OQ Protocol should address the following points: the function Test of HVAC (Heating-Ventilation-air conditioning) compared to the functional requirements specified alarms critics locking alarms operating parameters critics defined on the data sheet of the room the standard operation for the cleanroom filter integrity Tests the air velocity and airflow models of air pressure Difference flow phase OOW should also address the worst-case scenarios.To design the worst-case scenario for the functioning of the clean room, the critical operating parameters are identified from the data sheet of the cleanroom.The operating range and the extreme beaches are defined for each critical parameter and the worst case is designed and documented.It should include the following: maximum and minimum Temperatures, maximum moisture and minimum maintenance Contamination of the scenario staff schedules the worst is usually run with specified Low settings and High specified.The output of this phase is a report OQ alarms and functional the cleanroom requirements specified in the specifications of the user.PHASE 4: QUALIFICATION of the PERFORMANCE qualification (PQ) the cleanroom performance goal is to demonstrate with objective evidence that the white room works consistently with defined parameters to produce the result environmental wished and defined.The qualification of cleanroom performance involves the testing and monitoring of the following: levels of suspended particles in the air levels of surface particles particles viable microbial humidity relative pressure differential Temperature phase exit PQ is a PQ report that analyzes the performance of the clean room using equipment settings specified.PQ is a pre-requisite for certification

CLEANROOM CERTIFICATION validated cleanrooms are validated for a required cleanliness class.The level of cleanliness that is chosen is determined by the needs of the users.Cleanroom classes are defined in ISO1464-1: methods for evaluation and measurement for certification are specified in ISO14644-3.He calls for the ten following tests. Test count of particles in the air Test of air flow differential air pressure leak Test of the Filter Test of visualisation of flow Test of direction of air flow temperature humidity recovery leak Test Test Test Test of containment once certified for a particular class, Cleanroom factors are monitored to ensure that the parameters do not have derived or changed and that the environment is under control.MONITOR and control a program of constant surveillance is required after certification.Compliance requirements are in the ISO 14644 - 2. ' statistical analysis for the parameters of cleanrooms is encouraged as a tool for monitoring of the white room after certification to ensure compliance.The tool of choice is statistical process control,