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 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 Principle:- To evaluate the manufacturers 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 Personnel Premises including personnel facilities Maintenance of buildings and equipment Storage of starting materials and finished products Equipment Production and in-process controls 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 The quality audit system mainly classified in three different categories : TYPES OF QUALITY AUDIT INTERNAL AUDIT To Ensure that adequate Quality systems are maintained To asses compliance with the C-GMPs 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 In a pharmaceutical facility for internal auditing, you require to check mainly two things namelyActivities carried out by different departments, Documents maintained by these departments EXTERNAL 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 . Carried Out by a company on its vendors or sub contractors No legal requirement for to conduct audit Regular audits will be carried out to assesses compliance with agreed standards Increase confidence in vendor auditing Reduce level of external auditing External auditors have experience of GMP and as well as regularly audited by their certification body REGULATORY AUDIT

Purpose of Regulatory audit:- Networking and confidence-building between national inspection authorities Development of quality systems Work towards global harmonization of GMP 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 483is given at the exit meeting ROLE OF GMP AUDITS IN Q.A AND Q.C PROGRAMMES What is to be audited:- Auditors review SOPs Employees Practices and behavior Compare master specifications against compendia 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 Assuring GMP compliance Detecting Potential Problems Effecting Programmed improvement Increasing management awareness Benefits which are derived from Audits are given below: ASSURING GMP COMPLIANCE FDA conducts routine inspections of all pharmaceutical manufacturers to determine if manufacturing and control procedures conform to GMP FDA investigators malke unannounced visits to the manufacturing facilities to excamine facilities , equipments, personnel and records Use systemic analysis approach DETECTING POTENTIAL PROBLEMS GMP audits find objectionmable condition that is unknown to responsible production , QC ,QA or management 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 manufacturing equipment or procedure Upgrading equipment or procedure Improving employee training programmed 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 appropriate step to eliminate the problem An audit is not finding any objectionable conditions Either there were no problems to be found Auditor failed to detect objectionable condition that were actually present ELEMENTS OF A SYSTEMIC AUDIT PROGRAM Key Elements Expectations and Philosophies Audit Formats and Approaches Checklist form GMP regulation approach System analysis methods Checklist written criteria and Standard Operating Procedures Planned periodic frequency for audit Specially trained personnel Finding Written Audit reports 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

AUDIT FORMAT AND APPROACHES:

Manual GMP audit methods can be divided in to categories AUDIT FORMAT AND APPROACHES 26

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. 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.

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. Disadvantages:GMP REGULATION FORMAT 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 The basic elements are derived from the following subpart of regulations SYSTEMIC POTENTIAL PROBLEM ANALYSIS Likely to Affect the Quality Of the Product These FDA investigators describe the organized method for determining of potential problem 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 . The responsibility for audit data review Personnel responsible for recommendation Decisions concerning corrective actions. Effective use of written criteria to ensure that conditions and practices remain under a suitable state of control SOPs should establish

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 Announced Visit: Advanced notice is given before the audit. It is not persuasive for two reasons Announced Visits: 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 pretion for the audit . Key personnel become available

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. Unannounced Audits Benefits :- Allows observation of normal condition and practices 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 firsthand experience dealing with GMP matters. Essential auditor skill is aware of Firms 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 The Audit objective Leader is usually a senior auditor who has extensive knowledge of the firms 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. 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:- Preliminary reports during the audit Final report to the management

Preliminary reports during the audit: Benefits can be gained from having dialogues with employees Finding is communicated with affected personnel. Discussion may help the employees to learn why problems happened. 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. Final report to the management SELF AUDIT QUESTIONS Does the company have a written self inspection procedures calling for self inspection at regular intervals? Does the procedure specify a designated expert or a team of experts to conduct regularly scheduled inspections? Does the self inspection schedule cover ail aspects of production? Does the self inspection schedule cover all aspects of quality control/quality assurance/ Does the self inspection schedule cover all aspects of the quality control laboratory? Is the follow-up action recorded?