Pharma Validation regulatory requirements.
Validation in Pharma Industry is very important part of Pharmaceutical Quality Managment System which in turn constitute quality assurance systems and intern Good manufacturing Practice guidelines. US FDA have given special emphasis on validation and it is prim requirement of US FDA prequalification, as well as all other pharma industry regulatory authorities world wide.
Because a pharmaceutical, food or drug product manufacturing facility is required to comply with Good manufacturing guidelines of US FDA other wise a drug or food product or pharmaceutical product being manufactured in a facility which do not comply with GMP guidelines is deemed to be adulterated and spurious, and concept of Validation in Pharma and Validation activity is given great importance in US FDA cGMP guidelines, therefore Validation has great importance pharmaceutical industry well as medical devices manufacturing industry.
Pharmaceutical Validation is a process of collection of documentary evidence and a process of demonstration that any of the procedure, process, methods, testing procedures or activity being adapted is capable of producing consistent and satisfactory reproducible result in terms of measurements or in terms of product quality. Therefore validation becomes a process of developing a procedure, method, testing procedure that yields consistent reproducible good quality desired result.
FDA gives emphasis on developing a process that gives consistency in results, this is a step towards assuring that the drug product being manufactured will by default will be of good quality by virtue of its adapted procedure. FDA do not want only a product that meets its final specification rather they ask for development of such procedures which gives consistently good quality product, this can be established or proved by process of validation of a pharmaceutical manufacturing process.
Inorder to demonstrate procedures gives consistently good quality product it is required that the systems itself and equipment are properly designed and qualified. To demonstrate that a pharmaceutical product manufactured with any process in any pharmaceutical company it is required to validate many procedures, processes, methods activities associated with pharmaceutical manufacturing including machinery , skills and testing procedures , methods.
Pharmaceutical Validation definition:
Validation can be defined as process of establishing through documented evidence a high degree of assurance that a specific process will consistently produce a product that meets its predetermined specifications and quality attributes. A validated manufacturing process is one that has been proven to do what it purports or is represented to do. The proof of validation is obtained through collection and evaluation of data, preferably beginning from the process development phase and continuing through the production phase. Validation necessarily includes process qualification (the qualification of materials, equipment, systems, buildings, and personnel), but it also includes the control of the entire processes for repeated batches or runs.
Types of Validation In pharmaceutical can be classified as follows
Cleaning validation is carried out to ascertain the procedure and method adapted for cleaning of equipments , and aria , is capable of giving desired cleanness , cleanliness of equipment can be ascertained by caring out trace analysis of active ingredient of previous products active ingredient trace analysis . by doing rinse water analysis or swab test, this is quite good method to ascertain the complete removal of earlier products residue so as to avoid cross contamination we have provided a complete example document for cleaning validation here.
Process validation is carried out on the manufacturing process or steps , which are adapted for during pharmaceutical manufacturing . The process adapted in pharma manufacturing should yield a consistent results with respect to quality of product. The laid down process is crosschecked for evidence for efficacy , and the results are documented for each step.FDA guidelines define process validation as follows
Process validation: The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products.
For example in manufacturing of tablets a final mixing step is validated by withdrawing samples from all points in mixer at intermittent intervals, and assay of active ingredients is done, results are plotted against respective sample points and time intervals, the ,most efficient time interval at which there are consistent and satisfactory result for desired content at all sampling point is considered to be the best for the process of final mixing step, and this best time interval point is again validated by crosschecking ,and documenting on further three batches. It is one of example of process validation, it can extend to other processes adapted in pharma manufacturing.
If there is any problem in the pharma manufacturing process just by analyzing the validation results one can know the step point or equipment or process which is responsible for any untoward result.
Types of validations in pharmaceutical: Following are the types in pharmaceutical validations
Prospective validation is process of gathering of data and documentary evidence about a product and its process before it is sent to market or for distribution, a new pharma product validation or a validation after making a change in the master formula, to determine if the product meet its predetermined standards. The process starts with designing of batch record , raw material specification and in process specifications and limits, establishing sampling plan, and equipment lists and required environment controls.
Is a validation process where in current production batches are used to confirm the compliance of processing parameters and standards. Concurrent validation is the set of validation procedures following prospective validation. Concurrent validation is carried out for ensuring the product batches produced in prospective validation meet the required standards and quality so that those can be distributed in market.
Concurrent validation is of great use when the test employed is not destructive and can determine the product meet predetermined standards and quality. Concurrent validation is also carried out on product or process which is previously validated process to ascertain that the product or the process meets required standards and is validated.
Retrospective Validation is a type of validation where in the product is already and established process such batches of products which are being sent to market are studied to gather documentary evidence about the efficacy of the process or any in process tests and the product it self, such type of validation can be adapted to validate product and the process even if the product and process is not validated earlier. It also makes use of data from old batches to establish the efficacy and compliance of product or process standards.
3. Analytical Method Validation
Here the method which is adapted to estimate the content, assay, purity or standard of a pharmaceutical product, tested for its efficacy and accuracy , that is it is assessed if the method adapted is capable of giving consistent and correct results without any error , even though there is change in chemicals, instrument or person .
The pharmaceutical analytical method adapted should be such that it should be able to detect the content, assay, purity or standard of pharmaceutical product without any error even if there is a change in change in chemicals, instrument or person and this has to be validated by crosschecking separately and documented as evidence for efficacy and efficiency of method adapted.
4.Computer System Validation:
The computerized system which are adapted in manufacturing of pharmaceuticals is tested for their worthiness , if the actual readings obtained from system , and those obtained in manually in process are both matching and are accurate and satisfactory so as to rely completely on the computer systems adapted in the process of pharmaceutical manufacturing and quality control , and quality assurance , and stores activity, rules governing computerised system validation , electronic signature and document generated through computerised systems are included in 21 cfr Part 11 of the United states code of federal regulations.
Pharma Validation Phases:
The activities relating to validation studies are classified into three phases:
Phase 1: Pre-Validation Phase or the Qualification Phase, which covers all activities relating to product research and development, formulation, pilot batch studies, scale-up studies, transfer of technology to commercial scale batches, establishing stability conditions, storage and handling of in-process and finished dosage forms, Equipment Qualification, Installation Qualification, master production documents, Operational Qualification, Process Capability.
Phase 2: Process Validation Phase (Process Qualification phase) designed to verify that all established limits of the Critical Process Parameters are valid and that satisfactory products can be produced even under the "worst case" conditions.
Phase 3: Validation Maintenance Phase requiring frequent review of all process related documents, including validation audit reports to assure that there have been no changes, deviations, failures, modifications to the production process, and that all SOP's have been followed, including Change Control procedures and qualifying systems ,equipment's are required to qualify for following Qualifications:
1.Design qualification (DQ)
2.Component qualification (CQ)
3.Installation qualification (IQ)
4.Operational qualification (OQ)
5.Process qualification (PQ)
Design Qualification (DQ)- It consists process of gathering documentary evidence of a particular instruments or machine’s fundamental operational and functional specification of an instrument , and its inherent program , or equipment and details about and its detailed design and its qualifications , why this instrument and is supplier chosen.
Installation Qualification (IQ) - It consists process of gathering documentary evidence and process of Demonstration that the process or equipment being installed complies with all of its qualifications of successful installation in a particular aria , so as to comply with intended requirements of process , with respect to its specifications, is it installed correctly, are all necessary accessories and components installed correctly and its documentation required for continued utilization are installed properly.
Operational Qualification (OQ) - It consists process of gathering documentary evidence and of Demonstration of all aspects of a equipment , process are functioning properly and accurately so as to yield intended ,measurements, results quality of a pharmaceutical being manufactured.
Performance Qualification (PQ) - It consists process of gathering documentary evidence and process of Demonstration of all aspects of a equipment , process are functioning properly and accurately so as to produce intended ,measurements, results , intended quality of a pharmaceutical manufactured over a period of time. in a consistent manner
Validation Master Plan,
It is a document which identifies and provides complete steps, guide or map or guidelines for caring out a particular validation procedure.
Where ever there is requirement of any validation , Validation procedure is first assigned a Validation Master Plan.
The Validation Process
It is a process of monitoring ,testing,and evaluation of all steps and process involved in a pharmaceutical manufacturing
Pharmaceutical Validation Protocol : All steps in pharmaceutical process are very important steps, and to ensure the process works with required standard pharmaceutical process validation is carried out, the complete details about validation process stages, procedures, and tests, standards, locations, persons responsible and undertaking or doing validation procedures, etc, the detailed road map detailed information of how to do things in a well documented format to carryout the validation procedure is termed as validation protocol, validation protocol also mentions, what should be done, if there is any deviation from the process, what should be done when the validation batches it self are required to be distributed to market and so on.
It requires that the software or programs which are utilized by pharmaceutical companies in manufacturing of pharmaceuticals should work without any error, it provides or leads to an accurate measures or activity .Example Dispensing of Raw Material using computerised system. Process control using a computerised system
In 21 CFR Part 11 this topic is covered in very detail and you can read it over here
Here screen shot prints are gathered to validate and document that the procedure adapted is leads to correct measures or activity
Complete details about Computer system Validation:
You will find complete guide for validation in pharmaceutical industry here
VALIDATIONS IN PHARMACEUTICAL INDUSTRY
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