Maximize the value of your cleaning validation program through holistic project management.In a world where information overload A symptom of the high-tech age, which is too much information for one human being to absorb in an expanding world of people and technology. It comes from all sources including TV, newspapers, magazines as well as wanted and unwanted regular mail, e-mail and faxes. is all too common, it is easy to succumb suc·cumb
intr.v. suc·cumbed, suc·cumb·ing, suc·cumbs
1. To submit to an overpowering force or yield to an overwhelming desire; give up or give in. See Synonyms at yield.
2. To die. to the temptation to narrow one's focus, ignoring anything that seems extraneous ex·tra·ne·ous
1. Not constituting a vital element or part.
2. Inessential or unrelated to the topic or matter at hand; irrelevant. See Synonyms at irrelevant.
3. . This attitude is often reinforced by certain organizational structures This article has no lead section.
To comply with Wikipedia's lead section guidelines, one should be written. that do not encourage personnel to look beyond their individual or departmental bailiwicks.
This compartmentalization comes at a cost, ranging from inefficiencies to outright errors and even injuries that might easily have been avoided. The good news is that by being cognizant of areas outside his or her traditional zone of awareness, the pharmaceutical project manager responsible for cleaning validation The introduction to this article provides insufficient context for those unfamiliar with the subject matter.
Please help [ improve the introduction] to meet Wikipedia's layout standards. You can discuss the issue on the talk page. can develop a program with a positive impact that reaches beyond compliance with GMPs.
Cleaning validation is a process validation based on well-defined processes with known critical process parameters and critical control points.
All cleaning process validation projects must incorporate and satisfy governmental regulations. They also must verify that a robust manufacturing unit operation that contributes to the organization's efficiency, effectiveness and profitability has been put in place.
This article describes the critical success factors necessary to develop and manage a successful cleaning validation project and addresses the business case concerns that an effective project manager must integrate. After all, a scientifically defined cleaning process and subsequent validation can yield the best solution for maximizing production capacity, minimizing downtime The time during which a computer is not functioning due to hardware, operating system or application program failure. and maintaining full GMP GMP (guanosine monophosphate): see guanine. compliance.
Science and GMP: The sine qua non [Latin, Without which not.] A description of a requisite or condition that is indispensable.
In the law of torts, a causal connection exists between a particular act and an injury when the injury would not have arisen but of cleaning validation.
Numerous tasks need to be accomplished in order to have a sound cleaning validation program and complete successful projects. Science and GMPs are key elements.
The first task is to understand and embrace the critical success factors in the creation of a cleaning validation program as embodied in a cleaning validation master plan. Those elements include both a well-defined cleaning process and a well-thought-out (and defendable) rationale for validation.
The cleaning process for a specific target entity starts with a scientific rationale and a risk-based approach to the entity. The question is, what risk does the entity pose to the product quality and the patient?
The answer will drive the critical process parameters and critical control points, which should be mapped and identified on a process flow chart. Development data or a scientific rationale is required to support the critical process parameter selection. Risk evaluation models can be used to determine the critical control points.
It is also necessary to identify the "edge of failure"--beyond which predictions of product performance are uncertain--in order to keep the process consistently within expected ranges without spending more time than necessary on cleaning. This step results in the most efficient cleaning cycle.
Additionally, analytical test methods must be developed to prove that cleaning has achieved the target requirements. The most efficient path to development of a successful cleaning program will leverage existing knowledge and processes in order to minimize redundant efforts and streamline the development process.
Finally, all of the above should be included in a comprehensive development report.
To be defendable, the rationale for validation must be based on defined processes There are two major approaches to controlling any process:
n.pr See acid, eicosapentaenoic.
n. , OSHA OSHA
Occupational Safety and Health Administration, a branch of the US Department of Labor responsible for establishing and enforcing safety and health standards in the workplace. regulations regarding chemicals and effluents related to the process, as well as FDA FDA
Food and Drug Administration
n.pr See Food and Drug Administration.
n.pr the abbreviation for the Food and Drug Administration. regulations regarding the effectiveness of the cleaning.
For the sake of simplicity, it makes sense to take a "family" approach for similar types of equipment and facility spaces, as well as for products with the same or similar target entities. In developing the master plan, it is important to consider (and document) a method for determining when more science is required for validation and when common sense is sufficient. Ultimately, the organization's risk tolerance Risk Tolerance
The degree of uncertainty that an investor can handle in regards to a negative change in the value of their portfolio.
An investor's risk tolerance varies according to age, income requirements, financial goals, etc. will determine the answers.
The master plan also must document how the selected analytical methods are validated, and it must outline roles and responsibilities for cleaning and validation.
In developing the plan, it is important to define the minimal prerequisites for the cleaning process so that cleaning validation can be successful. The elements described above provide a starting point Noun 1. starting point - earliest limiting point
terminus a quo
commencement, get-go, offset, outset, showtime, starting time, beginning, start, kickoff, first - the time at which something is supposed to begin; "they got an early start"; "she knew from the for determining whether a cleaning process has been defined to the point that it can be validated and that it meets the company's goals for production cycle times. If these key elements are not in place, it is not possible to achieve an effective and compliant cleaning process and subsequent validation.
Experience shows that defining the preliminary process elements is the largest part of the project. Once they are clearly defined, developing the cleaning validation protocol is simply a matter of identifying a sampling protocol that uses an approved cleaning procedure and test methods.
The bigger picture: looking beyond GMPs
The GMP elements described above are of utmost importance. They drive the foundation of the cleaning validation or, for that matter, of any technical project within an FDA-regulated industry. The successful project leader, however, also must address some other critical areas, including safety, environmental concerns and supply chain management.
For example: protecting personnel. The company has an ethical and legal obligation to safeguard its people from harm. Any industrial site must follow appropriate OSHA regulations, and part of the development of the cleaning process is ensuring that the process is safe. To do so, the site should employ the services of someone who is trained and educated in the area of safety and safety regulations. This person should perform an initial audit of the process, delineating safety concerns in detail as well as the resolution of any safety anomalies.
The safety expert's recommendations must be incorporated into the designs of the cleaning equipment, the cleaning process, the protective gear, the material flow, and the personnel flow and activity. The safety expert should perform a similar audit at the completion of the validation effort to ensure that the process has not strayed outside the real of safety regulations. Once the process is deemed safe, it can be available for routine implementation.
Watching wastewater: Many validated cleaning procedures incorporate the use of detergents and cleaning agents that may be detrimental to the bacteria and other microorganisms that consume organic matter in the wastewater treatment plant Wastewater treatment plant also called wastewater treatment works
waste from an abattoir carried away in liquid form. Disposal is a major problem because of the need to avoid pollution of waterways. See aerobic effluent treatment, anaerobic effluent treatment. to ensure that it meets EPA requirements as well as any applicable state and local environmental regulations.
To accomplish this, the cleaning process should include measures to neutralize neutralize
to render neutral. the pH of the outgoing water stream. This piece of the engineering puzzle should be addressed at the beginning of the project and designed into the equipment and process chain of events. It makes sense to validate the effluent neutralization neutralization, chemical reaction, according to the Arrhenius theory of acids and bases, in which a water solution of acid is mixed with a water solution of base to form a salt and water; this reaction is complete only if the resulting solution has neither acidic nor step, although this is not a GMP requirement. It is beneficial to ensure the effectiveness and repeatability of this step, as it will ensure compliance with environmental laws and help position the company as an environmentally responsible organization.
Enhancing efficiency: The cleaning validation project can have a major impact on supply chain management, including its subset, manufacturing resource planning Manufacturing Resource Planning (MRP II) is defined by APICS as a method for the effective planning of all resources of a manufacturing company. Ideally, it addresses operational planning in units, financial planning in dollars, and has a simulation capability to answer (MRP (Material Requirements Planning) An information system that determines what assemblies must be built and what materials must be procured in order to build a unit of equipment by a certain date. ) or enterprise resource planning See ERP.
(application, business) Enterprise Resource Planning - (ERP) Any software system designed to support and automate the business processes of medium and large businesses. (ERP (Enterprise Resource Planning) An integrated information system that serves all departments within an enterprise. Evolving out of the manufacturing industry, ERP implies the use of packaged software rather than proprietary software written by or for one customer. ). The project's impact is potentially the greatest in the areas of materials management Materials management is the branch of logistics that deals with the tangible components of a supply chain. Specifically, this covers the acquisition of spare parts and replacements, quality control of purchasing and ordering such parts, and the standards involved in ordering, and capacity management.
The need to manage the cleaning detergent is a materials management issue. The project team must embark on a series of tasks in order to manage the detergent successfully in the site's inventory and raw material systems. First, the team must identify the detergent to be used in the operation. Next, the team must assign the detergent a code number and create an MRP item master that is compatible with the site's inventory system. Quality control testing specifications must be established, and analysts must be trained on the testing procedure.
Capacity management also benefits from attention during the cleaning validation project. One of the beautiful results of a well-run validation exercise is that is can yield a tremendous amount of data that can be used to quantify the equipment cleaning and preparation unit operation.
Every cleaning cycle that is validated supplies the site with data that can be associated with each batching vessel or piece of equipment that is to be cleaned. If the validation reports, SOPs, cleaning cycles, equipment and product are appropriately connected, it is possible to calculate labor, time and detergent consumption based on the production schedule for the year. Doing so will provide excellent data for budgeting and resource scheduling, as well as for measuring the capacity utilization Capacity Utilization measures the rate at which a firm makes use of their capital productive capacities, such as factories and machinery. Capacity Utilization generally rises when the economy is healthy and falls when demand softens. of the unit operation. As a result, management can rely on quantifiable data, rather than estimates, to orchestrate or·ches·trate
tr.v. or·ches·trat·ed, or·ches·trat·ing, or·ches·trates
1. To compose or arrange (music) for performance by an orchestra.
2. the area. The process is simple, and the project manager can incorporate the exercise into the cleaning validation project plan.
For example, suppose a site a validated a cleaning cycle for its 200-liter stainless steel stainless steel: see steel.
Any of a family of alloy steels usually containing 10–30% chromium. The presence of chromium, together with low carbon content, gives remarkable resistance to corrosion and heat. tanks, which the company uses for only one of its products. The company will produce 100 batches of the product in a year, and it uses one tank per batch. In addition, the project summary report states that the following cycle is validated:
1. Charge the tank with 100 L of water for injection (WFI WFI Wide Field Imager
WFI Water For Injection
WFI Wireless Facilities Inc.
WFI Workforce Florida, Inc.
WFI WaterFurnace International
WFI Wraparound Fidelity Index
WFI Water For Irrigation
WFI Washington Food Industry (Olympia, WA) ).
2. Add 1 L of clean-in-place (CIP (1) (Common Isochronous Packet) The packet format used in time-based (real time) FireWire transmission. See FireWire, IEC 61883 and mLAN.
(2) (Common Industrial P ) detergent.
3. Attach recirculation Noun 1. recirculation - circulation again
circulation - the spread or transmission of something (as news or money) to a wider group or area loop per SOP "X."
4. Heat the solution to 80 degrees and recircluate the solution for 90 minutes.
5. Drain solution.
6. Charge tank with 100 L of WFI.
7. Recirculate the WFI for 10 minutes.
8. Drain solution.
9. Charge tank with 100 L of WFI.
10. Recirculate the WFI for 10 minutes.
11. Drain the solution.
12. Dry the tank with filtered air for 20 minutes.
It is possible to calculate the annual consumption of WFI and detergent, as well as the approximate number of hours that the site will need to dedicate to equipment cleaning, based on the information known about the cycle and the production schedule. In this example, WFI usage will equal 3,000 liters annually, and detergent usage will equal 100 liters per year. 100 batches per year X 300 L WFI per batch = 3,000 L WFI annually. 100 batches per year X 1 L CIP per batch -100 L detergent annually.
Conclusion: Real-world consequences
The concepts presented here are not revolutionary, but all too often organizations neglect to apply them--sometimes with dire consequences. At one site, for example, an operator who was following a validated cleaning procedure was blinded for several hours when the pH 12 cleaning solution he was using splashed and hit him in the eye. The injury could have been avoided had the cleaning procedure he was following instructed him to wear goggles goggles,
n the protective eyewear worn by dental personnel and patients during dental procedures.
see periocular leukotrichia. and protective gear and to perform the tasks with another person present. In another case, an operator cleaned the hatch gasket on a tank by allowing the highly alkaline cleaning solution to overflow in an uncontained manner.
The spill contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. exposed pallets of raw material in the adjacent storage areas. Although the employee was being diligent, he did not understand the consequences of his actions. Had the company had an internal safety expert reviewing the cleaning process, the unsafe condition might have been avoided
Another company caught the at of the EPA and local environmental regulators when the site discharged its pH 12 cleaning solution directly into the city wastewater system. The company could have avoided the problem--and the fines--by designing a neutralization unit operation downstream of the cleaning process.
Yet another company performed its GMP responsibilities admirably and released the new, validated cleaning cycles to the appropriate operations. After a week, equipment was backed up because site personnel could not clean it fast enough.
In today's lean, mean pharmaceutical marketplace, companies need every advantage to gain an edge over the competition. To that end, the savvy project manager will consider areas within the organization that are impacted by, and can be incorporated into, the cleaning validation project, in order to support overall operational success and not just GMP compliance.
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Critical Success Factors for a Cleaning Validation Master Plan
Some key items that the project manager should include in a Cleaning Validation Master Plan:
* Regulatory references
* Process development report requirements
* Analytical method requirements
* IQ, OQ and PQ requirements for equipment and systems
* CIP system validation
* Manual cleaning validation requirements
* Acceptance criteria/specification rationale
* Clean hold time validation requirements
* Micro-testing requirements
* Minimum number of successful sequential runs required for consistency
* Record times, temperatures, volumes, sequences (run approved process at worst-case end of ranges as applicable)
* Operator qualification and training requirements
* Protocol & Summary Report requirements
* Re-qualification program requirements
* Sustainable deliverables
Editor's note Editor's Note (foaled in 1993 in Kentucky) is an American thoroughbred Stallion racehorse. He was sired by 1992 U.S. Champion 2 YO Colt Forty Niner, who in turn was a son of Champion sire Mr. Prospector and out of the mare, Beware Of The Cat.
Trained by D. : Andy DiFelice, Technical Director and Senior Consultant, IPS (1) (Inches Per Second) The measurement of the speed of tape passing by a read/write head or paper passing through a pen plotter.
(2) (IPS) (Intrusion Prevention S , spoke at a Nov. 14 Expertbriefing titled "Cleaning Validation Critical Success Factors."
By Andy DiFelice and Chuck Stock, Integrated Project Services (IPS)