The APIC Audit Programme tb final comments 5 Oct 06

Walter

Description

The Revised APIC Audit Programme Standardised Audits Cost Reduction APIC-certified Auditors GMP Compliance Evaluation A Third Party Audit Programme for MA Holders and API Manufacturers Coordinated by API Compliance A sector group of Institute www.api-compliance.orgNecessity for API Manufacturers to Comply with cGMP for APIs - Legal Background - According to the revised EU legislation ‘the holder of a manufacturing authorisation shall at least be obliged to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials’ (Directive 2001/83/EC as amended, article 46(f)for Human Medicinal Products and Directive 2001/82/EC, article 50(f) for Veterinary Medicinal Products). The competent authorities expect that the manufacturing authorisation holder will carry out an audit of the manufacturers/distributors of the active substances concerned. One of the primary means by which the competent authorities will determine whether manufacturing authorisation holders are in compliance with the above requirements will be the ‘examination, by inspectors, of the audit programmes used by authorisation holders for conducting regular audits (every 2-3 years), including review of ...

Informations

• Publié par: Nuther
• Nombre de lectures: 18
• Langue: English

Extrait

The Revised APIC AuditProgramme

A Third Party Audit Programme for MA Holders and API Manufacturers

A sector group of

Standardised Audits

Cost Reduction

APIC-certified Auditors

GMP Comliance Evaluation

Coordinated by

API Compliance Institute

www.api-compliance.org

Necessity for API Manufacturers to Comply with cGMP for APIs -Legal Background - According to the revised EU legislation‘the holder of a manufacturing authorisation shall at least be obliged to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials’(Directive 2001/83/EC as amended, article 46(f)for Human Medicinal Products and Directive 2001/82/EC, article 50(f) for Veterinary Medicinal Products). The competent authorities expectthat the manufacturing authorisation holder will carry out an audit ofthe manufacturers/distributors of the active substances concerned.One of the primary means by which the competent authorities will determine whether manufacturing authorisation holders are in compliance with the above requirements will be the ‘examination, by inspectors, of the audit programmes used by authorisation holders for conducting regular audits (every 2-3 years), including review of audit reports’ (see Compilation of Community Procedures on Inspections and Exchange of Information;Guidance on the occasions when it is appropriate for Competent Authorities to conduct inspections at the premises of Manufacturers of Active Substances used as starting materials, Doc.Ref. EMEA/INS/GMP/3351/03/Rev 5 from 23 June 2006). What is the "APIC Audit Programme"? The “APIC Audit Programme”is a third party audit programme for auditing API manufacturers, distributors and API contract manufacturers and/or contract laboratories. This programme was initially developed and has now been revised by APIC/CEFIC in line with the European Authorities guidances. The API Compliance Institute will coordinate the audit process. The Qualified Person(s) of Manufacturing Authorisation Holders will take the lead in initiating requests for Third Party Auditsof API Manufacturers and reviewing the impact of any Deficiencies found. The Compliance Triangle Principle as illustrated below is followed at all steps of the audit process. The API Manufacturer can also initiate the Third Party Audit for the purposes of a SelfAssessment of their GMP Compliance.

API Manufacturer

QP(s) of MA Holder(s)

API Compliance Institute

Auditors

It is the aim of the APIC Audit Programme to offer anindependent andrecognised GMP Compliance auditof API manufacturers and/or distributors, including organisation, conduct and evaluation of the audit. APIC audits will be conducted worldwide. The participation in the “APIC Audit Programme” is on voluntary basis and not limited to members of APIC.

Who can initiate a Third Party Audit? The following chart describes three scenarios where a Third Party Audit can be initiated and shows the corresponding costs.

AP ICThird Party AuditP rog ramme The 3Alternatives

Third Party 1 AuditAP IC

S hared 2 Third Party AP ICAudit

S elf- 3 As s es s ment AP ICAudit

Initiated by a QP of a manufacturing authoris ation holder

Initiated by more than one QP of different manufacturing authoris ation holders

Initiated by an API manufacturer

Duration: 2 Days Number of Auditors :2 Cos t:€ 8,400.- net, plus travel expens es

Duration: 2 Days Number of Auditors: 2 Cos t:Depending on the number of companies involved, e.g. 4 companies = € 2,300.- net per company, plus travelexpens es

Duration: 2 Days Number of Auditors: 1 Cos t:€ 4,200.- net, plus travel expens es

 Howcan GMP audits be standardised? There are three basic principles of the “APIC Audit Programme” for standardising audits: „ experienced and trained auditors that are registered as APIC certified auditors „ standardised process for preparing audits „ release of audit report byAPI Compliance Institute „ evaluation of audit findings by QP(s) or API Manufacturer in case of self assessment audit. The audits are conducted by APIC certified auditors „ who have the professional experience, „ who are independent , have not worked for theaudit customer(s) or auditeefor at least the previous 5 years and there is no conflict of interest „ who have completed an ICH Q7A compliance education course and a special APIC Auditor Training „ who have participated in recognised training courses/conferences on current GMP topics „ who have signed a contract laying down the obligations as an auditor in the framework of the APIC Audit Programme The audits are conducted on the basis of theEC GMP Guide Part II /ICH Q7A (GoodManufacturing Practice Guide for Active Pharmaceutical Ingredients)with regard to the APIC Auditing Guide.

Save money and optimise the GMP Audit The aims of The “APIC Audit Programme” are: „ standardised GMP audits of API manufacturers „ objective assessment of GMP Compliance Level and evidence / classification of any deficiencies found „ quality not quantity of audits to control audit burden for industry „ minimised costs by -decreasing the frequency of audits and sharing costs when more than oneQP areinvolved in the audit process -standardised costs for audits Will Third Party Audits be Accepted by the Authorities? EU Authorities According to theGMP Questions and Answers page on the EMEA website on audits of Active substances manufacturers, anyaudit should be performed by properly qualified and trained staff, the scope should cover the relevant GMP requirements, the audit must be properly documented and the audit report will be reviewed by the authorities during inspections of Manufacturing Authorisation Holders. If a Third Party Audit of the active substances manufacture is arranged, the Contract Giver (in this case the QP of the MA Holder) must evaluate the Contract Acceptor (Audit organisation) and the Auditors to ensure that the Third Party Audit will be as effective as an audit performed directly by the MA Holder and also ensure there is no conflict of interest. If these principles apply,Sharing of Third Party Audits are acceptable to the Authorities as long as each MA Holder satisfies themselves that the scope of the audit is applicable to the API’s used as Starting Materials in the manufacture of their Medicinal Products. FDA Similar third party programmes have already been established in other areas. With regard to the acceptance of Third Party Audits IPEC memberIrwin Silversteinsaid "lawyer with both industry and FDA experiencehave been involved in developing the program and (that) nobody has raised a concern that the third party audit would present more of a problem than having your own people do the same audit". (Gold Sheet, Vol 34, No. 1, January 2000).

The "APIC Audit Programme" - Step by step - „ Request by QP / API Manufacturer (Customers) for Third Party Step 1: Initiating Phase Audit to API Compliance Institute (ACI) „ ACI provides details of APIC Audit Programme QP(s) of MA Holder „ Customers evaluate audit process and decide if it meets their requirements „ ACI discusses potential involvement of other QP(s) with initiating ACI API QP / API Manufacturer to evaluateSharedThird Party Audit Manufacturer Auditors Option „ Pre-Audit Questionnaire sent to API Manufacturer by ACI „ ACI informs the API Manufacturer (Auditee) and the QP(s) of the Step 2: Selection of Auditors proposed APIC Certified Auditors. Both the API Manufacturer QP(s) of MA Holder and/or the QP can refuse one or both auditors (e.g. due to competition reasons) „ Auditors declare independence from Customer/API Manufacturer and sign obligation to Protect Confidential ACI information in Secrecy Agreement API Manufacturer Auditors „ Audit Agreement is signed by All Parties involved „ Customer may define specific points to be covered by auditors in amendment to agreement „ Lead Auditor interacts directly with the API Manufacturer in order to plan the audit in detail keeping the QP(s), co-auditor and ACI informed „ Systematic audit of GMP Compliance is performed (Standard - QP(s) of MA Holder Two days, two auditors); APIC Audit Aide Memoire referenced to ICHQ7A is available to assist auditors „ Overall Results of Audit, Explanation and Classification of any AC GMP Deficiencies is given to API Manufacturer in Closing Meeting API Manufacturer Auditors „ Lead Auditor sends the draft audit report to the API Manufacturer for review and response to any GMP Deficiencies „ API Manufacturer sends updated report with response to any audit observations to Auditors and ACI QP(s) of MA Holder ACI API Manufacturer Auditors „ Auditors check that response has been received for each Audit Deficiency and sign Audit Report that is sent to ACI „ ACI sends copy of signed Audit Report to Customer/QP(s) and API Manufacturer QP(s) of MA Holder „ QP(s) decide if audit deficiencies have been properly addressed and on GMP Status of the API used in Manufacture of their Medicinal Products ACI API Manufacturer Auditors Third Party Audit Process now complete IMPORTANT: As the APIC Audit Programme is a worldwide third party auditing programme the audits will be conducted in English and the Audit Report will be written in English.

The APIC Audit Programme – More Details For more Information about the APIC Audit Programme please ask for the APIC Audit Programme booklet which contains a detailed description of the programme as well as the necessary contracts. You will find the contact address at the bottom of this page. Classification rating Urgency Key for Classification of observations The condition will seriously affect the quality of products, Serious zzz regulatory compliance. The condition violates essential GMP- rules and basic quality assurance practices. Immediate action should be taken. The condition may affect the quality of the product, regulatory zz compliance. The condition violates GMP-rules and quality Major assurance practices. Action is recommended. The condition may not affect the quality of the product, , z Minor regulatory compliance. The condition violates current GMP- rules . R Recommendation for quality, safety or efficiency improvement. No GMP violation. Recommendations The Auditors In general,the audits will be conducted by two auditors who are registered as APIC Certified Auditors (exception: Self Assessment Audits). APIC Certified Auditorswill undergo extensive training programmes as described in this brochure and have to verify their professional experience. APIC will authorise a register of certified auditors who are allowed to conduct the audits within the framework of the “APIC Audit Programme”. Validity The basic audit report isvalid for three years. Follow Up Audits QP(s) or API Manufacturer will decide on need for follow up audit and timing of next periodic audit. Costs The average costs for a GMP Audit conducted by two qualified APIC auditors will be€ 8,400,-- plus VAT, plus travel expenses. The costs for Shared Third Party Audits will be divided basedon the number of companies involved plus a handling fee of €200 per customer, e.g. 4 companies = € 2,300,- Plus VAT, plus travel expenses. Contact If you are interested in joining The APIC Audit Programme, please contact us for further information:

OR Dr Gerhard Becker P.O. Box 10 17 64 69007 Heidelberg, Germany Phone [phone] - 84 44 0 Fax [phone] - 84 44 34 E-mail: [e-mail] www.api-compliance.org

Mr Pieter van der Hoeven, CEFIC Active Pharmaceutical Ingredients Committee (APIC) Av. E. Van Nieuwenhuyse 4 / box 2 1160 Brussels, Belgium Phone [phone] Fax [phone] E-mail : [e-mail]