Jump to top navigation | Jump to main navigation | Jump to content
Therapeutic Goods Administration logo

Audit of medicine manufacturers

Introduction

The Manufacturer Assessment Section (MAS), formerly GMP Auditing and Licensing Section, of the Therapeutic Goods Administration (TGA) is responsible for licensing of Australian manufacturers and audits of Australian and overseas manufacturers wishing to supply therapeutic goods in Australia.

With certain exceptions, manufacturers of therapeutic goods in Australia are required under the Therapeutic Goods Act 1989 to hold a licence. To obtain a licence to manufacture therapeutic goods, a manufacturer must demonstrate compliance with manufacturing principles including Codes of Good Manufacturing Practice (GMP) <http://www.tga.gov.au/docs/html/gmpcodes.htm>. Each Code of GMP sets out requirements relating to quality management, premises, equipment, personnel, documentation, process control, and quality control. To ensure that products are consistently of high quality, GMP auditors monitor compliance with the Codes by carrying out regular on-site audits.

Overseas manufacturers that supply therapeutic goods to Australia are also required under the Therapeutic Goods Act 1989 to meet at least an equivalent standard of GMP as Australian manufacturers. To avoid the need for an on-site audit by the TGA, sponsors may submit an acceptable form of evidence of the standard of manufacture for assessment (GMP clearance) when applications are lodged for listing/registration of medicines - see the Guidelines on Standard for Overseas Manufacturers.

Audit frequency and scheduling

The frequency of audit of manufacturers of therapeutic goods is based on the degree of risk to patients and consumers in relation to the extent to which a manufacturer complies with GMP and the type of products manufactured, as well as a range of other risk factors.

Some of the risk factors taken into account when scheduling audits are:

  • Type of products manufactured
  • Result of previous GMP audit
  • Product recalls since last audit
  • Medicine adverse reaction reports
  • Product complaints since last audit
  • Results of product testing by TGA Laboratories or other agencies
  • Surveillance / Enforcement reports impacting on GMP
  • Adverse comments from other agencies that have an impact on GMP
  • Significant changes within the company, eg. changes to key personnel, buildings, key equipment, products, intention to cease business etc.

Generally, the audit frequency is between 12-24 months (depending on the previous GMP compliance rating) for the high risk category, 12-30 months for the medium risk and 12-36 months for the low risk category. A GMP compliance rating is assigned after the manufacturer's response to the TGA audit report has been assessed.

New licence applicants will be scheduled for audit as soon as possible after receipt of the licence application. However, scheduled audits of manufacturers that were found at the last audit to have minimal compliance ratings will take priority over new manufacturers.

Top of page

Audit duration

Generally an audit may take part of a day or up to several days and involves a detailed examination of the operations and procedures of the factory. It is important that the initial audit of a new manufacturer be thorough and comprehensive; a minimum of two full days is therefore usually allocated to a full-step manufacturer audit.

For on-going audits, the Lead Auditor will decide the duration of the audit, taking into account:

  • previous Lead Auditor's recommendation;
  • the level of compliance of the last audit; and
  • the risk factors as outlined above.

Audit team

An audit team will consist of a Lead Auditor and may include, where appropriate, one or more auditors and/or one or more technical specialists in the relevant technology and manufacturing processes. The Lead Auditor is in overall charge of the team and is responsible for leading the opening and exit meetings with the company, and preparing the deficiency as well as the final GMP audit reports.

As the initial audit of a new manufacturer need to be comprehensive, it sometimes requires more than one auditor and/or relevant technical specialists.

Technical specialists are selected from an approved list of specialists who have been assessed by an independent panel chaired by the Chief GMP Auditor. The specialists are required to have appropriate academic qualifications and/or technical training.

The audit team may also include auditor trainees or observers who are acceptable to the auditee and Lead Auditor. Observers are not considered to be auditors, but are still bound by obligations of confidentiality.

Typical TGA audit of a medicine manufacturer

Before the audit:

  • Lead auditor is assigned.
  • The audit team is decided.
  • Lead auditor notifies the company - no earlier than the week before the audit. An unscheduled audit may be considered where it is believed that the true extent of GMP compliance cannot be assessed otherwise.
  • Audit team reviews documentation including Site Master File.
  • Lead Auditor prepares an audit plan for use by the audit team.

At the audit:

  • Lead Auditor chairs an opening meeting with the auditee's management:
    • Members of the audit team are introduced.
    • The scope and objectives of the audit are reviewed.
    • The audit plan is discussed.
    • A short summary of the methods and procedures to be used to conduct the audit is provided.
    • Communication links between the audit team and auditee are established.
    • It is confirmed that the resources and facilities needed by the audit team are available.
    • Arrangements for auditor caucus are made.
    • A tentative time and date for the closing meeting and any interim meetings of the audit team and the auditee's management are established.
    • The accuracy is verified, in the case of a pre-licence audit, of the licence application details, especially legal name of enterprise, site address(es) and nominated persons and scope of activities.
  • Audit is conducted.
  • Audit team meets to discuss and prepare a Deficiency Report (laptop computer).
  • Exit interview with the company:
    • Lead Auditor gives overview of the audit and its outcome
    • Lead Auditor may provide the company with the Deficiency Report and encourages discussion.
    • Lead auditor requests written response to the Deficiency Report within 4 weeks from the date of receiving the report. Objective evidence of corrective action is required for critical and major deficiencies.
  • Retention samples may be taken for TGA Laboratory testing.

After the audit:

  • Written Deficiency Report not provided at the exit interview is provided to the company within five working days.
  • Lead auditor reviews company's response to the audit report. If the response is acceptable, the audit is closed out.
    • If the response is unacceptable, it is referred to an independent internal Review Panel (comprising the Chief/Deputy Chief GMP Auditor and at least two other independent members - usually GMP auditors). The Review Panel may consider various actions such as early re-audit, amending licence conditions, licence suspension, licence revocation, dispute resolution, etc.
  • Lead Auditor sends final audit report and advises the company of the outcome.
  • Audit reviewed internally.

Appeals and complaints

The Therapeutic Goods Act 1989 provides an appeal mechanism against decisions that may adversely affect the viability of manufacturing licences. However, companies that are not satisfied with the auditor's decisions are encouraged to initially seek a review by the Chief GMP Auditor.

Complaints about auditing or against an auditor should be referred to the Chief GMP Auditor for appropriate action.

Top of page