Quality Control and Quality Assurance

Legible

All paper and electronic data must be legible and permanent. Ensuring records are legible and permanent assists with its accessibility throughout the data lifecycle including the storage of paper and electronic data.

Complete

All paper and electronic data, including original test results and repeat tests results, must be properly recorded clearly identifying the person performing the test as well as the when the test was performed

ALCOA(+)

Attributable, Legible, Contemporaneous, Original, and Accurate Complete, Consistent, Enduring and Available (CCEA) was added in 2010 Used by regulated industries as a framework for ensuring data integrity and is essential to ensuring Good Documentation Practices (GDPs).

Data Integrity

ALCOA+, essential component of the industry's responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA's ability to protect the public health

Attributable

All paper and electronic data must be attributable to the person generating the data including who performed an action and when. Can be accomplished by recording manually, by initialing and dating a paper record, or by audit trail in an electronic system.

Control Objectives

1. You must establish standards. 2. You need to measure performance. 3. You compare the measured performance to the established standards. 4. Take corrective action as needed. And most important is to ensure that the corrective action taken is effective.

483 observation

Clear, specific and significant. Made when in the investigator's judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.

QC (quality control)

Confirmation in verification aspect of quality management. Test products to make sure that they meet specifications. Set of activities for ensuring quality in products. The activities CONFIRM that attributes as stated for the product are met. o If the attributes are not met, then activities focus on identifying defects in the actual products produced (BEFORE products is released to the market place). Reactive process.

QA (quality assurance)

Confirms that the quality control test for a specification and is confident that this product can be released into the marketplace. Set of activities for ensuring quality in the processes by which products are developed. Aims to prevent defects with a focus on the ENTIRE process used to make the product. It is a proactive quality process. Goal is to implement processes so that defects do not arise when the product is being developed.

QS objectives

Customer Needs: Functional, Safe and Relevant Product Regulatory Needs: establishing and maintain compliance. Business Needs: Be efficient and effective in manufacturing.

Available

Paper and electronic data are required to be readily available for review, audits, or inspections for the required lifetime of the record. Paper and electronic data should be clearly indexed and/or appropriately labeled to facilitate retrieval.

Document Control

keeping document organized and ready to retrieve, as well as ensuring they are to be reviewed and signed off on. You want all documents to be legible. You want them to be signed and typically will be reviewed, especially in the case of environmental monitoring data.

483

FDA Form presented and discussed with the company's senior management at the conclusion of an inspection. Notifies the company's management of objectionable conditions.

risk assessment

Typically, a review of your systems to see how you match up against what you should be doing and what are the potential risk involved.

contemperaneous

means to record the paper or electronic data at the time it is performed. Date and time stamps should flow in order of execution for the data to be credible. Data should never be back dated, or forms completed with expected results prior to execution

Accurate

the data should be free from errors, complete, truthful, and reflective of the observation. Editing should only be performed by using the principles of GDPs.

483 topics

• Absence of Written Procedures-always follow the rule, "do that is written and write what is done" • Data Integrity Issues- data must be secure and accessible to authorized personnel only • Failure to Investigate Discrepancies (not adequate investigation) always conduct a proper and thorough investigation for each and every incident • Cleaning and Maintenance- proper documentation must be in place to identify the "hold" time period for cleaned equipment and the time period the equipment can be used without re-cleaning • Environmental Monitoring- a lot of data is generated during monitoring of facilities. You must do something with the data and it is best to create frequent summaries

Quality Management Goals

• control the sources of product quality variation • ensure the correct and most appropriate manufacturing and packaging practices are being followed • assure that the testing results comply with the standards or specifications • assure product stability for products in the market place

Consistent

The data's sequence of events should be in the expected sequence of operations and appropriately date or time stamped to demonstrate the data are contemporaneous

Original

The paper or electronic medium in which the data point is initially recorded including protocol, form, notebooks, spreadsheet, database, or software application. Understanding where the original data is generated to ensure content and meaning are preserved

GDP Basics

All entries must be clear and legible Never make erasures or write overs. Any written error must be crossed out in such a manner that the original information is still legible The crossed-out section must be initialed and dated by originator. Corrections must be made adjacent to the deleted entry. Write reason for correction (eg Transposition, Illegible entry, Scale zero error) Never vary your initials or signature. Use only black or blue permanent ink. The ink should not run or smear if the record is splashed with liquid. All entries must be permanent and able to be photocopied. When portions of a page or a complete page remain unused, a single line must be drawn angularly across the unused portion. Sign and date the crossed out section and provide an explanation Ensure the pagination (all pages to be numbered; could be page X of Y for loose sheets and page x.. For bound books) Make the required entries on the record as the work is performed. Do not record information on a separate piece of paper /temporary entry and enter on the record later

Data Integrity Observations

Backdating/Postdating/Missing Signatures Fabricating/faking data Copying existing data as new data Releasing failing product Hiding/obscuring SOP or protocol deviations Not saving electronic or hard copy data Inadequate reporting of failure and deviation Use of non-validated software Mismatch between reported data and actual data No links/traceability to source documents or original data. Re-running samples / Test until release/ No /Inappropriate Audit Trail Inadequate Access Authorization/ Privileges Discarding Deleting of data/ omitting negative data (like OOS or eliminating outliers) Not reporting failing results /stability failures Conducting unofficial analysis Disabling audit trails in electronic data capture systems Fabricating training data Having unofficial batch sheets and analytical reports

QS Process aproach

Goal is to understand and meet the requirements of your quality system. These requirements are typically internal specifications or guidelines that you hope to accomplish within your quality system. Periodically assessing your system allows for the monitoring of the performance and effectiveness of your systems. The outcome of these assessments will help you to make improvements. Four aspects to focus on. The planning, the doing, the checks, and the Act. • Plan: Establish objectives and processes to deliver the results. Critical that these objectives are communicated. • Do: Implement the processes • Check: Monitor and measure process and product against all of the elements of the PQS • Act: Take actions to improve process performance

Enduring

Paper and electronic data are appropriately recorded in laboratory notebooks or in validated software systems including spreadsheets and databases

QC (quality control)

Part of the quality management system focused on fulfilling quality requirements.

QA (quality assurance)

Part of the quality management system focused on providing confidence that the quality requirements will be fulfilled.

Robust Quality System

Procedures are in place and the company is following the procedures, testing according to the procedures, and meeting all the specification within procedures.

Management Control

Purpose is to provide adequate resources for device design, manufacturing, quality assurance, distribution, installation, and servicing activities; assure the quality system is functioning properly; monitor the quality system; and make necessary adjustment.

QC responsibilities

Responsible for the day-to-day control of quality within the company Responsible for analytical testing of incoming raw materials and inspection of packaging components, including labelling Conducts in-process testing when required, perform environmental monitoring, and conduct the required tests on finished dosage forms Assists in the selection of qualified vendors from whom raw materials are purchased. Testing of representative samples is required, and in many cases, an audit of vendor's operations is necessary to determine their suitability and degree of compliance with GMPs prior to supplier approval. The environmental areas for manufacturing of various dosage forms are tested and inspected by this division.

QA responsibilities

Sets the tone for the Quality Culture of the company Responsible for ensuring that the quality policies adopted by a company are followed. Helps to identify and prepare the necessary SOPs relative to the organization and control of quality. Must determine that the product meets all the applicable specifications and that it was manufactured according to the internal SOPs and to the standards of current GMP principles Also holds responsibilities for internal quality monitoring, internal and external audit functions, and overall quality management.

GDP (Good Documentation Practices)

Standards by which documents are created and maintained and is a legal requirement that ensures the integrity and reliability of data.