Audits

1. Audits

2. Definition: • 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.

3. Reasons for quality auditing: • In order to internal: • Determine the level of compliance • Build confidence (hopefully) in GMP and the QA system • Build interdepartmental trust, understanding, and communication (if the audit is done properly and tactfully) • Determine measures necessary to improve, e.g.,: • Premises, equipment, environment • Operations, actions, procedures • Personnel/training • Provide a stimulus for improvement • Recommend corrective action • Monitor improvement

4. In order to external : • Establish and monitor capability of supplier or contractor to deliver goods and services that are fit for purpose (and on time, and in the quantity required) • Build mutual confidence • Promote understanding and communication between the parties involved (both sides can learn!) • And in general, as listed for “internal”

5. Scope and Objectives: • To ensure quality of the Product • To assess effectiveness of QA system • It permits timely correction of problems • It established high degree of confidence

6. Auditee : • An organization, facility or person being audit. Auditee’s Responsibility : • Inform relevant employees about the objectives and scope of the audit • Appoint responsible members of staff to meet with members of the audit team • Provide all resources needed for the audit team in order to ensure an effective and efficient audit process • Co-operate with the auditors to permit the audit objectives to be achieved • Determine and initiate corrective actions based on the audit report

7. Types of quality audit : • Internal audit • External audit • Regulatory audit • Product audit • Process audit • System audit

8. 1. Internal audit (First party) : • Purpose of internal audit: • Increase the potential for early identification of regulatory concerns based on FDA interpretations and current compliance focus • Identify compliance deficiency and deviations from industry standards and company requirements • Provide a benchmark of compliance with other companies and regulatory expectations. • Inform management about regulatory risk • Foster continuous improvement and forward quality • Provide a tool by which the company can stay ahead of rapidly increasing regulatory demands

9. Benefits of internal audit : • Tells you the health of a quality system • Identify the root of a problem and plan for corrective and preventive actions with timeline • Achieve better allocation of resources • Able to avoid potentially big problem • Continuous improvement

10. Designing of internal audit system : • In pharmaceutical industry mainly two things required to check, 1. Activites carried out by different departments 2. Documents mainted by these departments Implementing the internal audit system : • Constitution of team • Provide initial training • Fix and audit schedule • Carry out the audit • Report the audit results • Follow up

11. 2. External audit (second party or third party ): • External audits are audits carried out by a company on its vendors or subcontractors. • Furthermore, if work is contracted out, they must ensure that contractors are competent to complete it, in accordance with GMP. • There are also strong business benefits to be derived from performing these audits: - building knowledge and confidence in the partnership arrangement - ensuring that requirements are understood and met - enabling reduction of certain activities (eg. in-house QC testing of starting materials) - reducing the risk of failure

12. Second party : • Customer employee audit your company • Your employee audit a company which supplies your company with a product or service. Third Party : • A customer wants an audit of your company but wants your company to pay for it.

13. 3. Regulatory Audit : • These audits are carried out by regulatory bodies against relevant regulations for the manufacture and supply of pharmaceutical products. • National regulatory bodies, such as the Medicines Control Agency (MCA) in the UK and Food and Drug Administration (FDA) in the USA, are statutorily responsible for carrying out such audits. • These audits may be unannounced (MCA currently performs about ten per cent of its UK inspections like this) as manufacturers are expected to be complying with GMP at all times. • Regulatory bodies from other countries in which products are sold may also audit companies (ie FDA audits European manufacturers). • Regulatory inspectors are extensively trained and are knowledgeable and professional.

14. All MCA medicines inspectors are relevantly qualified and have a minimum of five years' appropriate experience in a manufacturing operation; • Failure to pass a regulatory audit can lead practical experience of GMP and receive to restrictions on (or the withdrawal of) a manufacturing or import/export licence ; • Regulatory audits vary considerably in scope, frequency and duration. Audits by the national regulatory body are likely to be regular and to cover systematically all areas of a facility, over a period of time.

15. Self-inspection and quality Audit : Principle:- • Purpose of self-inspection is to evaluate the manufacturer’s Compliance with GMP in all aspects of production and Quality control. •  The self-inspection programmed should be designed to detect any shortcomings in the implementation of GMP and to recommend the necessary corrective actions. •  Self-inspections should be performed routinely, and may be, in addition, performed on special occasions, e.g. in the case of product recalls or repeated rejections, or when an inspection by the health authorities is concerned. •  The procedure for self-inspection should be documented.

16. Items to be self –inspected : • 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; • Calibration of instruments or measurement system • Labels control; • Results of previous self-inspections and any corrective steps Taken

17. Self-inspection team : • Management should appoint a self inspection team constiting of experts in their respective fields and familiar with GMP. • The members of the team may be appointed from inside or outside. Frequency of self-inspection : • It may depend on company requirments but should preferably be at least once a year. The frequency should be specified in procedure.

18. Qualification of Auditors : • Auditors must have specific knowledge related to all steps of quality audit • They must be familiar with department in which he or she wants to carry out audit • The following is an example providing checklist of essential components : • General facilities : • Are operations performed within separate or defined areas of adequate size ? • Are change rooms designed and used so as to minimise contamination ? • Is there an adequate disposal collection system ?

19. Ware-Housing Areas: • Are there physical seperation between approved and rejected material stores ? • Are there separate stores for raw materials, packaging materials, labels and finishd products ? • Self-Inspection procedures: • Does the self inspection schedule cover all aspects of production , quality control, quality assurance ? • Is the area clean, neat and orderly ? • Do personal follow authorized written procedures regarding washing of equipment and facility ?

20. Organization and management : • Are personal instructed on sanitation and health requirements ? • Are the specified tests repeated annually and records kept ? • Are the head of production and head of quality control different persons neither of whom is responsible to the other ?

21. Tools of Auditor 1. Documents • Quality and GMP regulations, standards, and guidelines (local, national, and international) • Previous audit and follow-up reports • Auditee’s own documents and records • Audit checklists and aides memoires 2. The auditing plan. 3. check-list for auditing.

22. Audit observations • Basic general company information- • Plant location and environment. • Company management. • Organizational information. • Training methods. • List of vendors. • Out-sourcing and services. 2. Departmental conditions and practices • Systems- Quality system, Documentation and Document Control, Change control systems, HVAC, Water supply, Engineering maintanence and Services etc.,

23. Audit report A suggested structure for an audit report is: 1. Site or area audited 2. Date and time of audit 3. Auditor(s) 4. Objectives and purpose of audit 5. Personnel encountered (names and positions) 6. Changes since any previous audit (organization, premises, equipment, procedures, products, etc.) 7. Observations — in logical order 8. Corrective measures requested 9. Oral responses of auditee 10. Final conclusions

24. Internal Quality Audit Report Proforma

25. Follow Up & Corrective Action Report FOLLOW UP- • WHO-8.6- There should be an effective follow-up programme. The company management should evaluate both the self-inspection report and the corrective actions as necessary. • final phase of the audit CORRECTIVE ACTION REPORT- • the use of a simplecorrective action report is a simple and easy way of requesting action, receiving information on action taken, and keeping track of any followup required.

26. Standard phases of quality audit : Successful auditing . Preparation Performance Reporting Follow-up Select team Opening meeting Recording nonconfarmances Veryfication of corrective & preventive action Quality manual evalution Interviewing Result evalution Examination Audit schedule formulation Report distribution Discussion Re audit Closing

27. Audit Evolution • Old Way evaluates • Organization • SOP’s • Manuals • Documentation • Compliance • New Way evaluates • Availability of process data • Training efforts • Teamwork • Customer awareness • Quality cost analysis • Customer & Supplier involvement