Validation cleaning equipment process

Other manufacturing procedures requiring validation include cleaning, decontamination and sanitation (CDS) procedures developed for specific items of equipment/processing areas. Of particular importance is the ability of such procedures to remove bioburden. This may be assessed by monitoring levels of microbial contamination before and after application of CDS protocols to the equipment item in question. 

Validation protocols may include test parameters, product characteristics, production equipment specifications and settings, and decision points on what constitutes acceptable test results. Three types of validation protocols should be available during the PAI cleaning, manufacturing process, and analytical methods. Any data associated with a completed protocol should also be made available. Also, if there had been any retrospective validation, these data should also be available. 

From the point in the process where full GMP compliance begins, the excipient should be produced in qualified equipment using a validated manufacturing process and testing should be done using validated methods. Where production equipment is not dedicated, validated cleaning methods are also needed. Full GMP compliance is required no later than the final excipient purification step or the manufacturing step where the excipient molecule has been synthesized, whichever occurs later in the process. 

For a WFI or highly purified water system, the SIP/CIP method is usually applied. In an SIP/CIP system, sterilization and/or cleaning take in place in situ or without dissembling the equipment. Consequently, the result of sterilization and/ or cleaning is confirmed by the process parameters previously validated. Based on process parameters and their ranges previously determined by the process validation, the SIP/CIP process can be confirmed whether or not it is completely sterilized and cleaned. This is a typical application of the concept of validation. 

A significant aspect of compliance is validation of the process through qualifications of the equipment installation and operation, process validation and, recently, the development of a cleaning validation. There are summaries describing how to qualify the installation and operation of equipment, piping, valves and instruments [84], The process validation requires evaluating the critical steps, which effect the quality and purity of the final active drug substance [85]. This involves development of a protocol, which states how the validation is to be conducted and defines the data to be collected. The most important part of the protocol is the development of acceptance criteria for the results. 

Qualification activities are normally associated with buildings, facilities, utility systems (e.g., water, air handling, Clean-in-place/Steam-in-place (CIP/SIP), and compressed gases) major equipment (including laboratory instrumentation), whereas validation likely is in reference to those confirmatory tasks related to processes and analytical methods. In simplistic terms, validation (and qualification) can be defined as documented evidence that a process, activity, or piece of equipment can consistently meet its predetermined acceptance criteria and quality attributes. This section will be dedicated towards outlining the requirements for validation of manufacturing processes, as... 

During development of the manufacturing process, an experienced microbiologist should be consulted as to the potential for microbial contamination of the product. Issues may include the selection of appropriate pharmaceutical ingredients, the ability of the manufacturing steps to control microbial contamination, the validation of sterilization processes, the cleaning and sanitization of process equipment, the adequacy of... 

Process validation, including equipment qualification and reviews of batch records, processing, cleaning validation, and on-site experiences. 

Various types of validation generally required in biopharmaceutical manufacturing include process validation, facility and equipment validation, analytical method validation, software validation, cleaning validation and expression system characterization. Combined with other elements of cGMP, including lot release testing, raw material testing, vendor quality certifications, and vendor audits, the quality of product can be consistently assured. 

Cleaning validation tests are performed to ascertain the effectiveness of the procedure used to clean pharmaceutical processing equipment (e.g., blender,... 

All necessary activities and responsibilities for the qualification and validation are controlled and specified in this Validation Master Plan. Every step of the described validation program for facilities, equipment, processes, process controls, and cleaning is in accordance with the current European Community Guidelines for GMP and FDA, and the cGMP guideline for finished pharmaceutical manufacturers. All requirements in these directives are fulfilled in this validation process. 

The production of the API and finished dosage form is required to comply with GMP regulations discussed in Chapter 9 and Section 10.2. The quality system, quality control and validation of equipment and processes have to be developed and adhered to in the manufacturing process. Proper records and documentation are required to be kept in the forms of batch records, test records and manufacturing procedures. Reaction vessels and associated equipment must be calibrated, validated and cleaned to acceptable levels before being used this is especially the case for multi-product plants where more than one API is manufactured. 

Equipment used to produce biotech products should be qualified for design, installation, operation, and performance [15]. The aging and continued performance of re-used process materials such as column resins is an important consideration during the validation of a biotech process. Demonstration of microbial control during processing is also a critical component of process validation, particularly in difficult to clean equipment such as alBnity columns or ultrafiltration membranes. Finally, consistent and reasonable step yield of individual unit operations can be verified during consistency and commercial product manufacturing. 

Chapter 3 continues the themes developed in the first two chapters and applies to changes made to equipment. This is a topic of special interest to the FDA because in the processing of semisolid products, the equipment plays a pivotal role. The mixing of drags within the base media is highly affected by the process and mechanism of mixing used. Also, because of the nature of product manufactured, often the cleaning and validation of equipment become serious issues. 

Tanks used in processing liquids and ointments are equipped with fittings that can be dismantled and cleaned. Validated Clean-In-Place (CIP) equipment can be dismantled for periodic verification. 

Three different batch sizes were used, namely =400, =800, respectively =1200 kg in the chemical industry it is standard practice to validate a process for the available kettles and then adjust the particular batch size (minimum filling so the stirrer bar remains covered, maximum filling so no overpressure occurs and vents stay free) to achieve the requested tonnage often, campaigns of batches are run before the equipment is cleaned and refitted for the next product, see batch numbers 19. .. 23, followed by 1,. ... ... 

Shifflet, M. J. and Shapiro, M., Validation of a cation-exchange method to test for residual amounts of a cleaning and sanitizing solution on pharmaceutical process equipment, BioPharm, 51, Jan. 2000. 

All production processes, such as ampoule washing and sterilization, solution filtration, equipment set-up and operation, sorting, and freeze-drier cleaning and operation, should be covered in detail in a procedure manual to ensure that all operations are understood as well as carried out properly and uniformly. Cleaning, sterilization, sterile filtration, filling, and aseptic processing operations must be validated. 

Facilities and Equipment System This includes (1) buildings and facilities along with maintenance (2) equipment IQ, QQ, calibration, maintenance, cleaning, and validation of cleaning processes and (3) utilities such as HVAC, compressed gases, steam, and water systems. 

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