PHARMACEUTICAL MANUFACTURING COMPLIANCE & GMP SUPPORT

Australian medicine manufacturers generally need to comply with applicable TGA manufacturing principles and PIC/S GMP requirements.

Relevant ICH guidance may also apply across areas such as pharmaceutical quality systems, quality risk management, product development, analytical validation and stability.

The exact requirements depend on the medicines, manufacturing processes and activities performed at the site.

A pharmaceutical quality system should connect the controls used across the manufacturing operation, including document control, deviations and CAPA, change management, qualification and validation, batch records, quality control, batch release, training and materials management.

These systems should work together so manufacturing activities are controlled, traceable and supported by appropriate evidence.

HCPA can help review, develop and strengthen these systems around your manufacturing operation.

GMP establishes the manufacturing standards that Australian manufacturers need to meet. The current PIC/S GMP Guide has legal force in Australia through the manufacturing principles.

ICH guidelines provide internationally harmonised scientific and quality guidance covering areas such as pharmaceutical development, quality risk management, quality systems, analytical validation and stability.

The TGA states that adopted international scientific guidelines are generally guidance rather than legislation, although relevant deviations may need to be justified.

ICH Q10 provides a model for a pharmaceutical quality system across the product lifecycle, including commercial manufacturing.

It covers areas such as process and product monitoring, CAPA, change management and management review of the quality system. The TGA has adopted ICH Q10 in Australia.

Equipment and systems need appropriate qualification, while manufacturing processes need validation where required under GMP.

PIC/S GMP Annex 15 addresses qualification and validation requirements for facilities, equipment, utilities and processes.

Records need to provide evidence of how materials were received and tested, how products were manufactured and controlled, the tests performed and the outcomes of relevant stability studies.

Australian legislation also sets specific retention requirements. The TGA states that applicable manufacturing records generally need to be retained for at least 12 months after the product expiry date, or at least six years after manufacture where there is no expiry date, subject to any longer GMP requirement that applies.

Batch documentation should allow the manufacturing history of the batch to be understood and traced, including materials used, manufacturing steps and controls, test results, deviations and information supporting release.

There is no single inspection interval for every manufacturer.

The TGA uses a risk-based inspection model that takes account of the product and process risk and the manufacturer’s compliance history. Changes to operations, buildings, equipment, product lines or key personnel can also affect the manufacturer’s risk profile.

Start by reviewing each deficiency, its classification and the timeframe for responding.

Then control any immediate risk, investigate the root cause and develop the corrective and preventive actions required to address the finding.

HCPA can help investigate the deficiencies, prepare the CAPA and organise the TGA inspection response.

A pharmaceutical compliance specialist with GMP experience can help investigate the deficiency, identify the root cause and develop a practical corrective and preventive action plan.

HCPA can support the investigation, remediation and preparation of the regulator response. Where enforcement action or legal rights are involved, legal advice may also be appropriate.

For critical and major GMP deficiencies, the CAPA should address:

• the root cause of the deficiency
• corrective actions addressing that root cause
• preventive actions
• corrections to examples identified during inspection
• responsibilities and completion dates
• evidence demonstrating implementation

The plan should be practical enough to implement and maintain within the manufacturing operation.

The TGA normally provides manufacturers of medicines and biologicals with up to four weeks to respond after receiving the post-inspection letter.

Shorter timeframes may apply where serious or significant compliance issues have been identified, so the timeframe in your specific TGA correspondence should always take priority.

The TGA classifies deficiencies according to their potential impact on product quality and patient safety.

A critical deficiency represents the most serious level of non-compliance and requires immediate attention. Major deficiencies are significant non-critical failures, while other findings still need to be corrected and addressed.

It depends on the severity of the findings, the manufacturer’s compliance history, the risks involved and the TGA’s assessment of the response.

Some findings may be closed through an acceptable response and supporting evidence, while more serious issues may lead to further inspection or scrutiny.

Yes. Serious GMP non-compliance can affect the manufacturer’s compliance status and may lead the TGA to consider regulatory action, including suspension or cancellation of a manufacturing licence.

Acceptance of the response does not end the compliance work. Corrective actions still need to be implemented as committed and their effectiveness maintained.

The TGA may review that effectiveness during a future inspection, so ongoing GMP compliance should become the focus once remediation is complete.