A Seminar On Quality Audit M.Pharm (Quality assurance) Prepared by :Paras Shah Guided By :Mr. Dhaval Rathod Contents Definition Objectives Difference between Quality audit and Periodic evaluation Self inspection Types of Quality Audit Role OF GMP Audit in QA and QC programmes Elements of a Systemic Audit program 1.Quality Audit Quality Audit Quality audit is defined as a systematic and independent examination to determine whether activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve objectives Quality audit means a systematic examination of a quality system. Quality audits are typically performed at defined intervals Any failure in their proper implementation may be published publicly and may lead to a revocation of quality certification 2.Objectives Of Quality Audit Pharmaceutical manufacturers commonly use audits as an effective mechanism to verify compliance with GMP regulation (GMP).GMP audits with two important goals Audis are intended to verify that manufacturing and Control systems are operating under a state of control. Audits permit timely correction of potential problems. Audits can be used to establish a high degree of confidence to remain under an adequate level of control by managements 3.Difference between Audit and Periodic Evaluation Quality audit Periodic Evaluation Quality audit is Periodic, independent, and documented examination and verification of activities, records, processes, and other elements of a quality system to determine their conformity with the requirements of a quality standard such as GMP Auditors should not have direct responsibilities for the operations they review Periodic evaluations are routine reviews and assessments of the quality standards of each drug product that are made to determine the need for changes in drug product specifications or manufacturing or control procedures Employees who are directly responsible for system under review normally perform periodic evaluations Audit is the function of Quality assurance Periodic evaluation is a function of Quality control department Conti…. Conti…. Quality audit Periodic Evaluation To verify on a regular basis that a firms procedures and practices are in conformity with established SOPs and applicable GMPs Periodic Evaluation determine the need for change in product, specification or control procedures and implement it if necessary Auditors reviewed Sops, Employee practices And behavior to see how well they follow established SOPs It plays a primary role in Day-to-Day decision-making process used by QC unit Report is prepared by Q.C personnel Quality control management personnel usually prepared Periodic evaluations 4.Self Inspection Principle: To evaluate the manufacturer’s Compliance with GMP in all aspects of production and Quality control. Designed to detect any shortcomings in the implementation of GMP and to recommend the necessary corrective actions Performed routinely as well as on special occasions, e.g. in the case of product recalls or repeated rejections Items of Self inspection Personnel Premises including personnel facilities Maintenance of buildings and equipment Storage of starting materials and finished products Equipment Production and in-process controls To be Continued……… Quality control Conti.… Documentation Sanitation and hygiene Validation and revalidation programmes Calibration of instruments or measurement systems Recall procedures Complaints management Labels control Results of previous self-inspections and any corrective steps Taken 5.Types Of Quality Audit The quality audit system mainly classified in three different categories: i Internal Audits ii. External Audits iii. Regulatory Audits i.Internal Audit Purpose of Internal audit: To Ensure that adequate Quality systems are maintained To asses compliance with the C-GMP’s and firms standard operating procedure To achieve consistency between manufacturing and testing facilities To identify problems internally and Correct problems prior to a FDA inspection Types Of Internal Audit Tier One Tier Two Tier Three Carried out:- Staff of a section or department of company Local Quality assurance Group Corporate Compliance Group And External Consultant Purpose:- Require Short time and Focusing on house keeping and documentation Require Longer period and more focus on system than housekeeping More focusing for asses the readiness of regulatory audit Frequency:- More Less Less than tier two Qualification:- Receive Some basic training More exclusive training Highly trained and experienced or specialist with the expert knowledge of GMP Designing of the Internal Audit System In a pharmaceutical facility for internal auditing, you require to check mainly two things namely - Activities carried out by different departments - Documents maintained by these departments Implementing the Internal Audit Program Constitute a small team of experts Provide Initial training Fix Audit schedule (Carried out at least once in Six months) Report the Audit finding and report given to top management and Shows corrective actions Repeat the audit as per preplanned Schedule ii.External External Audit Audit Purpose of External Audit: Confidence in the partnership arrangement Ensuring that requirements are understood Enabling reduction of in-house QC testing of starting materials Reducing the risk of failure Conti…. Conti…. Carried Out by a company on its vendors or sub contractors No legal requirement for to conduct audit External auditors have experience of GMP and as well as regularly audited by their certification body iii.Regulatory Audit Purpose of Regulatory audit:Networking and confidence-building between national inspection authorities Development of quality systems Work towards global harmonisation of GMP Conti…. Conti…. Carried out by regulatory bodies such as MCA(U.K),USFDA(USA) for manufacturing and supply of pharmaceutical product Audits may be unannounced Failure of regulatory audit withdrawal of a manufacturing or import/export license After regulatory audit,a formal report will be delivered For MCA:- verbal feedback report is given at the exit meeting For USFDA:- Provides “Form 483”is given at the exit meeting 6.Role of GMP Audits in Q.A And Q.C programmes What is to be audited:Auditors review SOPs Employees Pracices and behaviour Compare master specifications against compendial and regulatory requirements Verify the test data and validation testing Validation test reports are compared against raw data Verify Corrective actions taken inreaction to audit finding Conti…. Conti…. Benefits which are derived from Audits are given below: Assuring GMP compliance Detecting Potential Problems Effecting Programme improvement Increasing management awareness Conti…. Assuring GMP Compliance FDA conducts routine inspections of all pharmaceutical manufacturers to determine if manufacturing and control procedures conform to GMPs FDA investigators make unannounced visits to the manufacturing facilities to examine facilities , equipments, personnel and records Detecting Potential Problems GMP audits find objectionmable condition that is unknown to responsible production , QC ,QA or mangement personnel. The auditor will see whether such actions are frequent or not .From this he can signal other GMP problems. Effecting Programme Improvements Changing SOPs Modifying maufacturing equipment or procedure Upgrading equipment or procedure Improiving emplyee training programme Developing new or revised documentary system Increasing Management Awareness For any given audits there are two outcomes,either problems are found or not If the problems are found , management takes an approprioate step to eliminate the problemn An audit is not finding any objectionable conditions Either there were no problems to be found Auditor failed to detect objectionble condition that were actuaslly present 7.Elements of a Systemic Audit Program Key Elements i. Expectations and Philosophies ii. Audit Formats and Approaches Checklist format GMP regulation approach System analysis methods iii. Checklist written criteria and Standard Operating Procedures iv. Planned periodic frequency for audit v. Specially trained personnel vi. Finding Written Audit reports i.Expectations and Philosophies Senior management establishes the fundamental expectations of audit Upper level management must establish the realistic goals and objectives Use of “ Formal Written Master Plan” approved by management ii.Audit Format And Approaches Manual GMP audit methods can be divided in to categories Checklist format GMP regulation approach Systems analysis method Checklist Format Use checklist as GMP audit guides and reporting finding. Series of questions or instructions are grouped in to logical order. Blocks may be used to record answer and space may be provided to make comments. Conti…. Conti…. Advantages: Simple, convenient and easy to use for any desired subjected area Knowledgeable personnel may develop questions and guideline Questions are in logical order that help auditor to detect problems Report can be prepared in a minimum amount of time. Conti…. Conti…. Disadvantages: Question may be interpreted in more than one way because of bias or hidden meaning Solve the devising questions is not easy task Limited content The amount and type of questions that are provided limited . Not every issue will be covered Each auditor must apply sound judgment when evaluating system. GMP Regulation Format The basic elements are derived from the following subpart of regulations Subpart B: Organization and personnel Subpart C: Building and facilities Subpart D: Equipments Subpart E: Production and Processing Controls Subpart F: Production and Packaging control Subpart H: Holding and Distribution Subpart I: Lab controls Subpart J: Records and Reports Subpart K: Returned and Salvaged drug Systemic Potential Problem Analysis Likely to Affect the Quality Of the Product These FDA investigators describe the organized method for determining of potential problem iii.Written Criteria And SOP Need to be established defining which audit data or elements are to be considered in the assessment of program performance Formal written SOPs should fully describe the details for carrying out the various audit functions. Effective use of written criteria to ensure that conditions and practices remain under a suitable state of control SOPs should establish The responsibility for audit data review Personnel responsible for recommendations Decisions concerning corrective actions. iv. Planned Periodic Frequency Each firm must establish the optimum time interval between audits based on several important factors like Intended purpose Objectives, scope and depth Prior history of audit finding. Two types of visit Can be done depending on the type of audit:Announced Visit Unannounced Audit Conti…. Announced Visits: Advanced notice is given before the audit. It is not persuasive for two reasons The employee covers up the problem. The person makes major adjustment in their behavior Benefits : Audit efficiency is improved from advance notification Necessary records may be organized and retrieved in the preparation for the audit. Key personnel become available Conti…. Conti…. Unannounced Audits To view conditions and practices that is normal or customary (representative) as possible. For observing employees behavior as well as observation of equipments and facilities. Benefits :Allows observation of normal condition and practices v. Specially Trained Personnel The following personnel factors deserve systemic attention Defining auditor Qualification Documentation training skills and Experience. Selecting audit teams Maintaining auditor awareness levels Defining Auditor Qualification Selected based On their knowledge Experience in manufacturing and QC principles as well as years of first hand experience dealing with GMP matters. Essential auditor skill is aware of Firm’s SOPs and Knowledge Integrated by various departments. Documentation Training Skills And Experience Two formats Scientific Principles Training under chemistry, engineering, statistical and pharmaceutics GMP GMP training may include the cumulative knowledge from years of experience This knowledge comes from Daily activities Formal training sessions Selecting Audit teams Limitations of Personnel audit Experience and knowledge, which is individual. Emphasize on familiar issues as well as particular area Team is required for cover many different systems and large amount of data. Composition of team will vary depending upon the nature and scope of the audit Conti…. Conti…. Leader is usually a senior auditor who has extensive knowledge of the firm’s operations and exhibit strong leadership qualities. Team size depends upon Firm size Total no of products manufacturing and control system Breath and depth of the audit. The Audit objective vi. Reporting Audit Finding Audit reports should contain complete details of the program detected. Corrective action is taken to eliminate problems and to measure the overall adequacy of the audit program uses reports. There are two important reporting phases:1) Preliminary reports during the audit 2) Final report to the management Conti…. Conti…. Preliminary reports during the audit: 1) Benefits can be gained from having dialogues with employees 2) Finding is communicated with affected personnel. 3) Discussion may help the employees to learn why problems happened. Conti…. Conti…. Final report to the management Management must review the final reports and determine what steps need to be taken to eliminate deficiencies. Management should sincerely encourage detection of problems and express appreciation for being able to improve quality operations. The audit reports may be shared with manger supervisor who may discuss finding with employees. The workers and supervisory personnel should be given the opportunity to explain their views and ideas about the audit findings. References Pharmaceutical Dosage forms:Parenteral medication,Revised and Expanded.Edited by Kenneth E.Avis,Herbert A.libermann and Leon Lachmann,Volume –3, Second edition , Page no:-363-420 Pharmaceutical Quality group mpnograph no:-5 (revised): Pharmaceutical Auditing , IQA2001,ISBN 0906810 68X Conti… Conti…. Quality asuurance And Quality management in pharmaceutical Industry By Y.Anjaneyulu,R.Marayya,Pharma Book syndicate, Page no:-209-218 Provisional Guideline ON the inspection of the pharmaceutical manufacturers in: WHO Expert committee on specification for Pharmaceutical Preparations: 32ndreport,Geneva,WHO,1992,Annex-2(Who technical report seried. No:-823)