Risk Management
/ By Panorama Consulting & Engineering Inc. / Audits and Process Improvements/ 0 Comments

Risk Assessment

Many people interchange hazard and risk on a daily basis. Unfortunately, they are actually two different concepts. The difference may not be as much as an issue for the everyday conversation, but when it comes to risk assessment and control, it is extremely important. Below you will gain a better understanding of the difference between the two and why the difference is so important.

The basic difference is that a hazard is something that will cause harm, while a risk is the possibility that a hazard may cause harm. Although they are used synonymously, knowing the difference could save your life or allow you to enjoy it more thoroughly.

In essence, a hazard will not be risky unless you are exposed to enough of it that it actually causes harm; the risk itself may actually be zero or it may be greatly reduced when precautions are taken around that hazard.

The simple relationship between the two is that you have to have exposure to a hazard to experience a risk. Thus, it is vital that you know the level of exposure you are going to have to the hazard to better understand how much risk is actually involved.

Risk Assessment Methods

There are a variety of risk assessment methods for the various categories. When it comes to the difference between hazard and risk, several categories may use different measurements and methods. As an example, the way risk is assessed in human health may be different from the risk assessment for project management.

Why Use a Risk Assessment Method?

A risk assessment is a tool used to determine the potential results from any given hazard. The assessment uses a combination of situational information, previous knowledge about the process, and judgments made from the knowledge and information.Since the risk is the potential damage done by a hazard, there are certain outcomes that any good risk assessment needs to have.

There are six main outcomes that are needed to have an effective risk assessment. By the end of the assessment you should know:

  • Any situations that may be hazardous
  • Which method is appropriate to use when determining the likelihood the hazard will occur
  • Alternative solutions for reducing and eliminating the risk or any negative consequences the may occur
  • More information for making a decision about risk management
  • Estimation for the uncertainly of the analysis

Steps of a Risk Assessment

Step 1: Discover the hazards. You can do this by using several different strategies such as walking around the area, navigating through portfolios and databases, or asking people who are around.

Step 2: Determine who may be harmed and how they may be harmed. After discovering the hazards you will need to determine who may be harmed by them, as well as how they may be harmed.

Step 3: Analyze the amount of risk and how you can control them. You may find that you can simply remove the hazard. If not, then decide which control method will be best to use to reduce the amount of risk.

Step 4: Document your assessment and results. It is important that you document what you find. This is done for legal reasons to protect you, the location, and any possible persons that may be involved. You also want to be sure that you write down your next plan of action – what control measures you are going to take.

Step 5: Regularly review and update your assessment. It is great to think that once the hazard is gone that all risks of harm are gone. This is not true. In some cases the hazard may return and in other new hazards may develop. Regularly checking will keep you and everyone around safe.

Risk Control Methods

Knowing the difference between hazard and risk leads to risk control. Risk is controlled when your business takes actions that help eliminate safety risks as much as you are able to do so. If it is not possible to completely eliminate the risk, controlling your risk may mean that you are taking actions to minimize the risks and hazards within the work environment.

There are four main methods that can be used to eliminate or minimize these risks – avoidance, loss prevention & reduction, transfer, and acceptance.

1. Avoidance

This is by far the easiest way to control any risk. When you decide to use this method, you find all possibly hazardous activities and stop them. It is important that you remember when choosing this option you may also miss out on other opportunities and gains.

2. Loss Prevention & Reduction

Using this method you will reduce the frequency and severity of a specific loss. You may decide to increase security measures or improve maintenance, or you may create rules that require your employees to wear certain safety gear.

3. Transfer

When you choose this method you will create a contract with a third party to deal with that risk. A couple great examples would be hiring a security company to improve security or hiring a cleaning crew to ensure health hazards are cleaned up.

4. Acceptance

This last method is not to be taken lightly. When you feel that transfer or loss prevention & reduction methods are not necessary or are too excessive, this may be the option for you. However, it is important that you understand this could possibly be dangerous for your company. Undergoing too many losses or enduring too many negative consequences can quickly sink your business.

/ By Panorama Consulting & Engineering Inc. / Utility Optimization/ 0 Comments

RESOURCE OPTIMIZATION

In today’s industrial age, where manufacturing processes are highly crucial and a synonym of development and growth, the need to use resources effectively and efficiently has become necessary. The continuous growth of industries has led to development of highly efficient or leaner processes which focus on minimum wastage and maximum utilization of the available resources through various technologies developed overtime. The use of robots and automating the processes in order to eliminate human error and increase efficiency has been adopted by almost every industry today which has further been facilitated by the Internet of Things (I0T) in developing smarter processes.

Utility optimization not only consists of handling resources in a smart manner, but also optimizing the path or manner in which they are handled. Adjusting the placement of machines as well as defining the flow of resources throughout the shop floor is also an integral part of the utility optimization process. An efficient flow ensures an efficient execution of process and minimum wastage of time and resources. This is usually done through the use of process flow charts do determine process steps as well as Pareto charts to determine the importance of every resource in terms of its usage and need in every process.

In order to execute resource optimization and make sure that it is continuously being carried out, energy audits and water audits can be done which track the energy needs of an organization and track the water consumption by the organization respectively. The audits not only provide feedback about the status of optimization within the organization, but also help in tracking the development in this area and accordingly set targets. Even though these audits are a bit time consuming but they are highly necessary as they help the organization stay aligned with their set targets.

Optimization of resource usage not only decreases the amount of waste generated, but also leads to greater profits and creates opportunities for recycling and reusing the wasted resources. In a lot of cases, resource optimization leads to a reduction in carbon footprint which is vital due to the currently degrading environmental conditions. Since India agreed to ratify the second commitment period (2013-2020) of the 1997 Kyoto Protocol for the reduction of Greenhouse Gases and thus reduce the carbon footprint, the need for cutting emissions and correspondingly minimizing waste through resource optimization has gained more importance. The rising trend of green technologies has facilitated in optimization as well as cutting down on energy usage and reducing emissions.

The whole world is currently progressing at an unbelievable rate and the environment is getting affected due to that very progress Resource optimization, hence, has become necessary not only for generating greater profits and minimizing wastage of resources, but also for sustainability.  “Recycle and Reuse” has become the motto for every major organization and new ways to optimize resource usage are constantly being researched and put into use. Since the progression of technology is inevitable, there will always be a great need for effective resource optimization processes which contribute to both- organization’s profits as well as sustainability.

Automated manufacturing Practice
/ By Panorama Consulting & Engineering Inc. / Audits and Process Improvements • Construction Management • Pharmaceutical Industry • Project Management/ 0 Comments

Good Automated Manufacturing Practice for Pharmaceutical Industries

The Good Automated Manufacturing Practice (GAMP) Forum was founded in 1991 by pharmaceutical industry professionals in the United Kingdom to address the industry’s need to improve comprehension and evolving expectations of regulatory agencies in Europe. The organization also sought to promote understanding of how computer systems validation should be conducted in the pharmaceutical industry.

GAMP rapidly became influential throughout countries as the quality of its work was recognized internationally. Over time, GAMP has become the acknowledged expert body for addressing issues of computer system validation.

GAMP’s guidance approach defines a set of industry best practices to enable compliance to all current regulatory expectations. More than simply a strict compliance standard, GAMP is a guideline for life sciences companies to use for their own quality procedures. As a result, it can be tailored to a number of computer system types.

Computer system validation following GAMP guidelines requires users and suppliers to work together so that responsibilities regarding the validation process are understood. For users, GAMP provides a documented assurance that a system is appropriate for the intended use before it goes live. Suppliers can use GAMP to test for avoidable defects in the supplied system to ensure quality product leaves the facility.

The GAMP framework addresses how systems are validated and documented. Companies do not need to follow the same set of procedures and processes of a GAMP framework to achieve validation and qualification levels that satisfy inspectors. Instead, GAMP examines the systems development lifecycle of an automated system to identify issues of validation, compliance and documentation.

As a voluntary program, GAMP offers both challenges and benefits. The top three challenges in implementing GAMP are establishing procedural control, handling management and change control, and finding an acceptable standard among the existing variations.

Establishing procedural control is a challenge in using GAMP guidelines because new frameworks may be necessary to gauge the validity of systems. Most pharmaceutical companies have already established a baseline that adheres to standards and regulations that exist today, but they may not have a procedure to check the processes that are in place. This could cause resistance among software developers who may prefer not to work within the confines of specifications and procedures developed by others. Specifications and procedures developed by previous software developers may hinder ways to adjust computer systems, but varying interpretations of GAMP guidelines allow for multiple solutions.

Another hurdle is change control. In the development or modification of computer systems, companies with even the highest of standards can suffer setbacks along the systems development lifecycle. Sometimes minor tweaks by the software programmer may cause breakdowns after validation changes have been implemented. Internal processes and procedures must be established to guard against these occurrences.

Effective documentation management is fundamental for compliance. Any inaccuracies or missing information renders all other efforts moot. Moreover, implementing a formal document management application may be cost-prohibitive for some organizations. Some companies simply use what’s in the GAMP checklists to evaluate their systems. Today’s environment demands a thorough process to show validation.

The benefits of utilizing the GAMP approach for both users and suppliers include:

  • Improved understanding of the subject with the introduction of common terminology
  • Reduced cost and time to achieve compliant systems
  • Reduced time and resources for revalidation or regression testing and remediation
  • Reduced cost of qualification
  • Enhanced compliance with regulatory expectations
  • Established responsibility for all involved parties

When the FDA introduced its current Good Manufacturing Practices (cGMP) for the 21st century initiative, companies shifted their approach to validation. Formerly, they only had to heed a set of rules that accounted for every piece of equipment that was used. Now they can take a risk-based approach to validation by addressing safety, efficacy and quality in the product considerations. This enables the industry to place its investments where it makes the most sense. The onus ultimately falls on manufacturers to accept greater responsibility to validate their systems having the attendant benefits of cost and time to market savings.

GAMP helps provide a quality product from the manufacturer, and helps to limit the pharmaceutical industry’s culpability by ensuring proper steps were placed to deliver a quality product through validated systems. By incorporating input from the full spectrum of stakeholders, fine-tuning and further development of the process is geared towards benefiting the life sciences industry and the general consumer market.

The tools exist for companies to take the steps needed to reap the benefits of validation. Understanding an early adoption of GAMP can increase a company’s competitive position, especially with the implementation of new technologies. By staying aware of technological innovations, companies are able to increase efficiency, minimize risks and reduce costs.

Plant Design
/ By Panorama Consulting & Engineering Inc. / System design/ 0 Comments

Plant design & engineering

From conducting Feasibility studies, FEED / Basic & Detail engineering during the engineering phase to providing field engineering services during construction & commissioning, a plant design & process engineering company & its services should span across the entire life cycle of projects.
Typical list of services covered under plant design & engineering include:

  • Conceptual and Techno-Economic Feasibility Studies
  • FEED & Basic Engineering
  • Pre-bid / Proposal Engineering
  • Preparation of Process Packages
  • Technology and Process Licensor Selection
  • Detailed Design & Engineering
  • Procurement & Construction Support
  • Field Engineering
  • De-bottlenecking studies and Trouble Shooting
  • Laser Scanning and 3D modeling
  • As-Built documentation
  • Decommissioning Studies

A company involved in process management & plant engineering carries out all the above activities. All the phases have to be carefully managed starting from Engineering Execution Strategy the FEED and defining the project baseline standards by establishing the codes to and procedures to be able to set Engineering Audit.

A plant design & engineering company has to maximize energy output and reduce LCOE. Since every project is different, Project specific factors such as the local irradiance, weather, soil, wind, and topography must be taken into account for the design, layout, technology selection, and system configuration.

By utilizing the plant design & engineering company’s industrial applications, facility owners will be able to more efficiently implement and execute the challenging plant design management processes.
Why Panorama as your plant design & engineering firm?

Panorama’s Plant Engineering team includes highly experienced engineers in the design and maintenance of industrial processing plants.

Our primary customer groups are those who are in the business of processing, refining, handling, manufacturing or treating petrochemicals, gases, water, waste, bulk materials, minerals, food products or manufactured products for use in other processes or for sale to others.

If you are looking to either expand your business, increase production, reduce bottlenecks, manufacture new products, improve efficiency, upgrade to new technologies, refurbish or repair – Panorama’s offering ranges from machine engineering and finite element analysis to fully integrated, multi-discipline industrial plant design.
Panorama utilises the latest 3D modelling software for each phase of project design development, from conceptual to definitive design, right through to the production of documentation for construction.

Panorama also customizes our delivery to suit the industrial plant company’s project development strategy – becoming accustomed to roles in a wide range of contractual relationships including: due diligence, design consultancy, independent inspection, EPCM, EPC, D&C, owner’s engineer, and strategic alliances.

Read more on what are the steps involved in Industrial Plant Design

/ By Panorama Consulting & Engineering Inc. / Chemical Industry • Pharmaceutical Industry • Process Engineering • Utility Optimization/ 0 Comments

Calibration for Pharmaceutical Industries

The pharmaceutical sector is governed by regulatory norms to ensure that quality standards are met for products in line with pharmaceutical cGMP guidelines. The FDA takes food and pharma production very seriously, which is why these guidelines are in place. Calibration is one such process wherein an instrument or a utility system is adjusted so that its readings are adherent to the defined guidelines. It is usually performed as per approved written procedures.
What is Equipment Calibration?
Equipment calibration is important as equipment is often used to gather critical data and hence calibrating them and keeping them up to date becomes mandatory. This process is carried out regularly since equipment used in pharmaceutical manufacturing depending on its functionality is subjected to a lot of wear and tear.Calibration is usually done component-wise to ensure accuracy of the operating equipment as per defined pharmaceutical cGMP.
Types of Calibration
Calibration types are defined as per the parameter which is crucial for a certain process. The classification is largely done on the basis of the type of reading, and common types include:
Pressure Calibration– This method calibrates pressure readings within barometers, transmitters, test gauges and other kinds of equipment commonly used in manufacturing setups.
Temperature Calibration– Calibration is done based on temperature readings, in simulation of a real-time environment. The equipment in this category includes furnaces, weather stations, bio repositories, thermistors, etc.
Flow Calibration– The calibration which is carried out routinely for flow meters that check product quantity or energy functions in processes. Some of the equipment which requires flow calibration includes flowmeters, rotameters and turbine meters.
Pipette Calibration– Pipettes are used in laboratories to measure liquids in small, precise quantities. This calibration method is utilized in labs that make frequent use of pipettes, and is a fairly stringent process since the degree of precision required is very high.
Electrical Calibration– This particular method is used for checking electrical equipment. The accreditation standards are set as per UKAS outlines, since these are considered the most accurate set of standards for electrical calibration.
Mechanical Calibration– Mechanical calibration checks for the accuracy of various measurements such as torque, mass, force, angle and vibration. All these elements are checked in a temperature-controlled facility, since variations in temperature can adversely impact the calibration process.
Since these instruments are used in real-time environments, they are subject to frequent wear and tear. However, they are used in processes that require a lot of precision in terms of data gathering and measured quantities.Therefore, in order to maintain the accuracy of the process and the measurements taken by equipment, frequent calibration is required.

The frequency with which equipment is to be calibrated depends on various factors such as:

  • The importance of the measurements for which instruments are used
  • The defined standards of the equipment manufacturer to adhere to the pharmaceutical CGMP guidelines.
  • The degree of risk involved in the process for which that equipment is being used
  • The degree of precision required from the equipment and the accuracy with which data is to be gathered from the equipment.
  • The extent to which the equipment is stable. This is evaluated from the historical data on the stability of the equipment

Calibration is a mandatory process in the pharmaceutical space considering the need for reproducible product quality. Lack of precision can lead to huge repercussions and penalties. Calibration forms an essential part of the quality assurance and validation process in the pharmaceutical industry.

Software Validation
/ By Panorama Consulting & Engineering Inc. / Audits and Process Improvements/ 0 Comments

Software Validation

Validation is a critical tool to assure the quality of computer system performance. Computer system software validation increases the reliability of systems, resulting in fewer errors and less risk to process and data integrity.
Computer system validation also reduces long term system and project costs by minimizing the cost of maintenance and rework.

Software Validation commences with a user requirement document (URS). URS is prepared to describe the critical functionalities those are required for our analysis. It is essential that the document is properly scoped in order that the procurement, installation, commissioning, validation, user training, maintenance, calibration and cleaning tasks are all investigated and defined adequately.

To scope and define an adequate validation procedure the URS has to be detailed sufficiently for various assessments to be made. The main assessment that concerns with qualification documentation is the risk assessment. This assessment is only concerned with ensuring that the degree of validation that is proposed; is compliant with the regulatory requirements.

So at this early stage it is required to execute a Validation Risk Assessment protocol against the end user’s requirements. This step is purely to ensure that the more obscure pieces of ancillary equipment and support services are fully understood and their requirement investigated, priced and included in the final issue of the URS; which will be sent out with the Request to Tender. This is an essential stage if the URS is to accurately define what depth and scope of validation is appropriate for the verification that the software will deliver all the requirement detailed in the URS.

The outcome of the Validation Risk Assessment (VRA) drives a split in software validation documentation scope, if the VRA categorizes the software validation as requiring Full Life Cycle Validation (FLCV); then a considerable amount of the software validation effort is put into establishing how the software originated, was designed and developed, in order to establish that its basic concept and development can be considered robust, sound and in accordance with best practices.

The original development plans; code reviews, methods reviews and testing plans must be available to enable this software validation documentation to be executed successfully. Once this proof of quality build is established, validation then follows a more convention path in inspections and verifications.

Software that is not classified as requiring FLCV treatment does not require this depth of verification into quality build history and is validated mainly by the more convention path in inspections and verifications.

Dynamic Testing

Dynamic testing verifies the execution flow of software, including decision paths, inputs, and outputs. Dynamic testing involves creating test cases, test vectors and oracles, and executing the software against these tests. The results are then compared with expected or known correct behavior of the software. Because the number of execution paths and conditions increases exponentially with the number of lines of code, testing for all possible execution traces and conditions for the software is impossible.

Static Analysis

Code inspections and testing can reduce coding errors; however, experience has shown that the process needs to be complemented with other methods. One such method is static analysis. This somewhat new method largely automates the software qualification process. The technique attempts to identify errors in the code, but does not necessarily prove their absence. Static analysis is used to identify potential and actual defects in source code.

Abstract Interpretation Verification

A code verification solution that includes abstract interpretation can be instrumental in assuring software safety and a good quality process. It is a sound verification process that enables the achievement of high integrity in embedded devices. Regulatory bodies such as the FDA and some segments of industry recognize the value of sound verification principles and are using tools based on these principles.

/ By Panorama Consulting & Engineering Inc. / Pharmaceutical Industry • Safety • System design • Utility Optimization/ 0 Comments

Utility Systems Qualification – Backbone for the Pharmaceutical Industry

Pharmaceutical manufacturing is a highly regulated industry. Given the stress on product quality and the widespread impact of substandard production on public health and safety, utility system qualification is a critical step that companies must take towards ensuring that all their products comply with federal laws and regulations.

In pharmaceuticals, critical utilities like WFI, RODI, Compressed Air, Nitrogen, Air Handling Units (AHU) and HVAC (Heating, Ventilation and Air Conditioning) systems support the manufacturing process. As a result, these are treated as products that need to satisfy FDA regulatory requirements and pharmaceutical manufacturing standards, just like raw materials and other equipment used in the industry.

Quantitative and qualitative specifications: Utilities must pass a string of qualitative and quantitative specifications to be considered satisfactory. Different utility systems have different quality and standard criteria, designed on the basis of inputs from relevant departments and organizations as well as manufacturing and engineering provisions. When a validation program is set in place for utility systems used in pharmaceutical, critical utilities should be first on the list. It’s important to focus on the design, qualification and monitoring of each utility system used in pharmaceutical or biotech companies, so their end product fulfills all pharmaceutical quality standards.

cGMP and FDA guidelines: Utility system qualification is designed to ensure that utilities in use conform to health and safety regulations, as well as pharmaceutical manufacturing standards and cGMP guidelines. Current good manufacturing practices (cGMPs) are FDA guidelines that check the design, control and monitoring of manufacturing facilities and processes. To comply with cGMP regulations, drugs and medicinal products need to be of the right quality, strength and purity, by way of adequately controlled and monitored manufacturing operations.

Steps in utility system qualification include:

  • Implementing strong operating procedures
  • Establishing extensive quality control systems
  • Procuring a consistent quality of raw material supplies
  • Maintaining dependable testing labs

If such a broad control system is implemented in a pharmaceutical facility, it can help to control:

  • Instances of mix-ups
  • Contamination, errors
  • Defects and deviations during the manufacturing process

Such pharmaceutical products are better able to meet public health and safety laws established by the FDA.

Flexibility: Pharmaceutical cGMP guidelines are flexible enough that all manufacturers are free to decide how to apply FDA controls in ways that fit their unique requirements. They can make use of a variety of processing methods, testing procedures and scientific designs to adapt their manufacturing processes to meet the laws. Because of the flexibility of these laws, companies can use innovative approaches and sophisticated technology to implement a system of continual improvement in order to achieve a consistent quality of pharmaceutical supplies.

FDA approved regulations: All pharmaceutical manufacturing facilities need to adhere strictly to FDA-approved regulations. Failure to meet FDA regulations can result in responsive action by the authorities against the product or the responsible facility, depending upon the seriousness of non-compliance. The company may have to recall the product under orders of the FDA, to ensure it does not cause additional harm or risk to the public.

cGMP requirements can be useful in ensuring the efficacy, quality and safety of pharmaceutical products by making sure facilities are in good operating condition, with sufficiently calibrated and well-maintained equipment, trained and experienced staff and reliable and efficient processes.

While a utility system cannot affect product quality on its own, it forms an integral part of the manufacturing process. That is where Panorama Consulting and Engineering, Inc. helps the companies setting up the validation processes as per the regulatory requirements.

/ By Panorama Consulting & Engineering Inc. / Pharmaceutical Industry/ 0 Comments

What is a Validation Master Plan?

A Validation Master Plan or a VMP is a document that outlines the principles and defines which processes and equipment need to be validated and the order of priority in which the same will be done. Validation of products, processes and facilities is an important part of a company’s Quality Management System(QMS). While the FDA doesn’t necessarily require a Validation Master Plan, it is often included in quality engineering services.A VMP should have logical reasoning for including or excluding every system associated with a validation project based on a risk assessment.
Pharmaceutical, biotechnology and medical device manufacturers are the key sectors that require a VMP. It is a key document in the GMP (Good manufacturing practice) regulated pharmaceutical industry as it drives a structured approach to validation projects.
The VMP is the foundation for the validation program and should include process validation, facility and utility qualification and validation, equipment qualification, cleaning and computer validation.The VMP is crucial from a quality and regulatory-compliance standpoint. At times, FDA inspectors may request documentation outlining an organization’s process and equipment validation plan. Thus, VMPs may help companies overcome challenges.

VMPs should include details of:

  • All prospective, concurrent, retrospective validation and revalidation activities
  • Time, location, priority and order of validation activities
  • A statement describing the validation policy of the company
  • An overview of the organization’s scope of operations, describing the facilities, products and processes
  • Facility management/personnel who have agreed upon the plan
  • Details or copies of any corresponding validation plans, existing SOPs, relevant policy documents and validation reports/protocols, etc.
  • Persons who are responsible and provide approval for SOPs, protocols and the VMP, as well as any review and reference tracking systems
  • References to or appendices detailing any plans for validation training programs.

Developing and implementing a VMP offers numerous benefits to manufacturers. A VMP is documented evidence that the manufacturer follows a well-defined strategy and has their validation process under control. This can be essentially useful during a quality system inspection. The VMP can also enhance business efficiency by preventing product or process failures and improving productivity.
VMP also leads to simplification of the validation process. VMP defines validation strategy and requirements, risk management and implementation. Thus, making the validation process simpler.
Operational excellence also benefits from VMP. A holistic approach helps define how the process will be integrated, how risk management will be applied and how validation will be handled for continuous improvement. It also defines how validation will be performed throughout the project life cycle and through regulatory submissions and other phased approval.
While the need of a VMP is not specifically required, it has become common practice in the pharmaceutical industry. The overall objective of a VMP is to ensure that quality requirements for processes and equipment are consistently met. When applied holistically, a VMP will simplify and standardize validation processes, facilitate continuous improvement and operational excellence, ensure smooth integration into quality systems, support design control and the device life cycle, and improve the overall cost of quality.
In conclusion, Validation is an excellent way to minimize risk and maximize production efficiency and quality. The extra cost incurred for validation is directly proportional to the level of risk aversion. Thus, a suitable validation program devised on pharmaceutical manufacturing standards would help build stability and efficiency.

Validation
/ By Panorama Consulting & Engineering Inc. / Audits and Process Improvements • Pharmaceutical Industry • Process Engineering • Safety/ 0 Comments

Validation Protocols for Pharmaceutical Industries

For pharmaceutical industries, product quality is paramount. Minor inconsistencies can lead to major disasters. To maintain quality assurance, consistency and risk assessment, industries conduct a validation of processes and equipment. A validation is a documented evidence of the consistency of processes and equipment. Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ) are an essential part of quality assurance through equipment validation.

DQ IQ OQ PQ protocols are ways of establishing that the equipment which is being used or installed will offer a high degree of quality assurance, so that manufacturing processes will consistently produce products that meet predetermined quality requirements.

Design Qualification (DQ)

Design qualification is a verification process on the design to meet particular requirements relating to the quality of manufacturing and pharmaceutical practices. It is important to take these procedures into consideration and follow them keenly. Along with Process Validation, pharmaceutical manufacturers must conduct Design Qualification during the initial stages. For DQ to be considered whole, other qualifications i.e. IQ, OQ and PQ need to be implemented on each instrument and the system as a whole.

DQ allows manufacturers to make corrections and changes reducing costs and avoiding delays. Changes made to a DQ should be documented which makes DQ on the finalized design easier and less prone to errors. By the use of a design validation protocol it is possible to determine whether the equipment or product will deliver its full functionality and conform to the requirements of the validation master plan.

Installation Qualification (IQ)

Any new equipment is first validated to check if it is capable of producing the desired results through Design Qualification, but its performance in a real-world scenario depends on the installation procedure that follows. Installation Qualification (IQ) verifies that the instrument or equipment being qualified, as well as its sub-systems and any ancillary systems, have been delivered, installed and configured in accordance with the manufacturer’s specifications or installation checklist. All procedures to do with maintenance, cleaning and calibration are drawn at the installation stage. It also details a list of all the continued Good Manufacturing Procedures (cGMP) requirements that are applicable in the installation qualification.

Conformance with cGMP’s requires, that whatever approach is used, it is fully documented in the individual Validation Plan. The IQ should not start with the Factory Acceptance Testing (FAT) or Commissioning tasks, but it should start before these tasks are completed; enabling the validation team to witness and document the final FAT and commissioning testing. The integration of these activities greatly reduces the costly and time consuming replication of unnecessary retesting.

These requirements must all be satisfied before the IQ can be completed and the qualification process is allowed to progress to the execution of the OQ.

Operational Qualification (OQ)

Operational Qualification is an essential process during the development of equipment required in the pharmaceutical industry. OQ is a series of tests which of tests which ensure the equipment and its sub-systems will operate within their specified limits consistently and dependably. Equipment may also be tested during OQ for qualities such as using an expected and acceptable amount of power or maintaining a certain temperature for a predetermined period of time. OQ follows a specific procedure to maintain thoroughness of the tests and accuracy of the results. The protocol must be detailed and easily replicated so that equipment can be tested multiple times using different testers. This ensures that the results are reliable and do not vary from tester to tester. OQ is an important step to develop safe and effective equipment.

Performance Qualification (PQ)

PQ is the final step in qualification processes for equipment, and this step involves verifying and documenting that the equipment is working reproducibly within a specified working range. Rather than testing each instrument individually, they are all tested together as part of a partial or overall process. Before the qualification begins, a detailed test plan is created, based on the process description.

Process Performance Qualification (PPQ) protocol is a vital part of process validation and qualification, which is used to ensure ongoing product quality by documenting performance over a period of time for a certain process.

Equipment qualification through DQ IQ OQ PQ practices is a part of Good Manufacturing Practice (GMP), through which manufacturers and laboratories can ensure that their equipment delivers consistent quality. It reduces the margin for errors, so the product quality can be maintained within industry standards or regulatory authority requirements. When qualification of equipment is not needed very frequently, performing it in-house might not be feasible, so smaller laboratories might benefit from scheduling external equipment validation services on a regular basis instead.

/ By Panorama Consulting & Engineering Inc. / Pharmaceutical Industry • System design/ 0 Comments

Design of Purified water & WFI Systems

Water is the one of the major commodities used by the pharmaceutical industry. It is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, active pharmaceutical ingredients (APIs) and intermediates, and analytical reagents. It may present as an excipient, or used for reconstitution of products, during synthesis, during production of finished product, or as a cleaning agent for rinsing vessels, equipment and primary packing materials etc.

There are many different grades of water used for pharmaceutical purposes. Several are described in USP monographs that specify uses, acceptable methods of preparation, and quality attributes. These waters can be divided into two general types: bulk waters, which are typically produced on site where they are used; and packaged waters, which are produced, packaged, and sterilized to preserve microbial quality throughout their packaged shelf life.

There are several specialized types of packaged waters, differing in their designated applications, packaging limitations, and other quality attributes.

Different grades of water quality are required depending on the different pharmaceutical uses.

Types of Water used:

Water is the most common aqueous vehicle used in pharmaceuticals. There are several types of water are used in the preparation of drug product, such as:

  1. Non potable water: It is water that is not of drinking water quality, but which may still be used for many other purposes, depending on its quality. It is generally all raw water that is untreated, such as that from lakes, rivers, ground water, springs and ground wells.
    Purposes:

    • cleaning of outer surface of the factory
    • used in garden
    • washing vehicles etc.
  2. Potable water: It is not suitable for general pharmaceutical use because of the considerable amount of dissolved solids present. These consist chiefly of the chlorides, sulphates & bicarbonates of Na, K, Ca and Mg. A 100 ml portion of water contains not more than 100 mg of residue (0.1%) after evaporation to dryness on a steam bath.
    Purposes:

    • To use as drinking water
    • Washing & extraction of crude drugs
    • Preparation of products for external use
  3. Purified water: It is used in the preparation of all medication containing water except ampoules, injections, some official external preparations such as liniments. It must meet the requirements for ionic & organic chemical purity & must be protected from microbial contamination.
    Purposes:

    • For the Production of non-parenteral preparation/formulation
    • For the Cleaning of certain equipment used in non-parenteral product preparation
    • For Cleaning of non-parenteral product-contact components
    • For All types of tests
    • For the Preparation of some bulk chemicals
    • For the preparation of media in microbiology

Water for Injection (WFI):

Water for Injection is a solvent used in the production of parenteral and other preparations where product endotoxin content must be controlled, and in other pharmaceutical applications.(WFI) is sterile, non pyrogenic, distilled water for the preparation of products for parenteral use.

It contains no added substance and meets all the requirements of the tests for purified water. It must meet the requirements of the pyrogen test. The finished water must meet all of the chemical requirements for Purified Water as well as an additional bacterial endotoxin specification.

Since endotoxins are produced by the kinds of microorganisms that are prone to inhabit water, the equipment and procedures used by the system to purify, store, and distribute Water for Injection must be designed to minimize or prevent microbial contamination as well as remove incoming endotoxins from the starting water. Water for Injection systems must be validated to reliably and consistently produce and distribute this quality of water.

Purposes:

  • For the production of parenteral products/formulation
  • For cleaning of parenteral product-contact components

Preparation technique:

  • Distillation
  • Reverse osmosis
  • Membrane process

Storage condition:

It can be stored for periods up to a month in special tanks containing ultraviolet lamps. When this freshly prepared water is stored and sterilized in hermitically sealed containers, it will remain in good condition indefinitely.

If autoclave is not available, freshly distilled water may be sterilized by boiling the water for at least 60 minutes in a flask stoppered with a plug of purified non-absorbent cotton covered with gauze, tin-foil or stout non-absorbent paper; or the neck of the flask may be covered with cellophane and tightly fastened with cord.

WFI System validation process:

How to preform WFI system validation in Pharmaceuticals and Acceptance Criteria for Water for Injection.

Process:

  1. Perform Installation Qualification. Verify piping, fittings, proper dimensions drawings, wiring, PC software, calibration, and quality of materials.
  2. Check flow rates, low volume of water supply, excessive pressure drop, resistivity drops below set point, and temperature drop or increase beyond set level.
  3. Perform general operational controls verification testing.
  4. Operate system throughout the range of operating design specifications or range of intended use.
  5. System regulators must operate within ±2 psi of design level.
  6. Operate the system per SOP for operation and maintenance of purified water system. Perform sampling over a 1 month period per the sampling procedure and schedule.
    Test samples for conformance to current USP Water for Injection monograph, microbial content and endotoxin content. Identify all morphological distinct colony forming units (CFUs) to at least the genus level
  7. Measure the flow rate and calculate the velocity of the water, or measure the velocity directly at a point between the last use point and the storage tank.
  8. Record the range of all process or equipment parameters (set points, flow rates, timing sequences, concentrations, etc.) verified during Operational and Performance Qualification testing.

Acceptance Criteria

  1. The system is installed in accordance with design specifications, manufacturer recommendations, and cGMPs. Instruments are calibrated, identified, and entered into the calibration program.
  2. General controls and alarms operate in accordance with design specification.
  3. The system operates in accordance with design specifications throughout the operating range or range of intended use.
  4. The system flow rate must be in compliance with design specifications.
  5. All samples must meet the following criteria:
    1. Chemical Testing: Test samples must meet the acceptance criteria of the chemical tests as described in USP Monograph on Water for Injection.
    2. Bacteriological Purity: All samples must contain no more than 10 cfu/100 ml; no pseudomonas or coliform are detected.
    3. Endotoxins: All samples must contain no more than 0.25 EU/ml.
    4. Physical Properties: The temperature of the hot Water for Injection must be greater than 80°C.
    5. Particulate Matter: Small Volume Injection: The Small Volume Injection meets the requirements of the test if the average number of particles it contains is not more than 10,000 per container that are equal to or greater than 10 µm in effective spherical diameter and not more than 1000 per container equal to or greater than 25 µm in effective spherical diameter.

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