Medicinal gases and good manufacturing practice (GMP)
Version 1.0, 25 May 2012
Good Manufacturing Practice (GMP) describes a set of principles and procedures that when followed helps ensure that therapeutic goods are of high quality.
The PIC/S guide to good manufacturing practice for medicinal products applies to medicinal gases. Interpretations of the PIC/S guide to GMP for medicinal gas manufacturers have been agreed by the TGA and the Australia New Zealand Industrial Gas Association.
Guide to interpretation of the PIC/S Guide to Good Manufacturing Practice for Medicinal Products – 15 January 2009; applicable to the manufacture of medicinal gases
- The following interpretations of the PIC/S Guide to GMP (15 January 2009) have been agreed between the TGA and the Australia New Zealand Industrial Gas Association. The tables will be updated as the need arises.
- Any questions about these interpretations, or requests for interpretation of any other clauses, should be emailed to firstname.lastname@example.org
|Version||Description of change||Author||Effective date|
|V1.0||New document. Replaces previous interpretation table on the TGA website for the Australian Code of GMP for Medicinal Products (16 August 2002).||Office of Manufacturing Quality||25/05/2012|
Medicinal gases are classified as medicines under the Therapeutic Goods Act 1989. The Manufacturing Principles 2009 determine that for the manufacture of medicines, compliance with the PIC/S Guide to Good Manufacturing Practice (GMP) - 15 January 2009 PE009-8 is required.
Schedule 7, entry 17 of the Therapeutic Goods Regulations 1990 exempts bulk liquefied medical gases from the operation of Part 3-3 of the Therapeutic Goods Act 1989.
Medicinal gas manufacturers have requested the TGA for additional guidance on the interpretation of the PIC/S Guide to GMP specifically for medicinal gas manufacture. After adoption at the time of the Australian Code of GMP (2002), which was based on the 2002 PIC/S Guide to GMP, the TGA has published a table on its web site summarising the interpretation of the Australian Code of GMP (2002) for medicinal gas manufacture.
Following the adoption of the 2009 PIC/S Guide to GMP, this guidance document has been developed in liaison with Australian medicinal gas manufacturers to replace that web site table.
Note: all clauses not mentioned in the table are fully applicable.
|1.4(i) to 1.4(xii)||
Product Quality Review (PQR)
New GMP section - relevant to medicinal gas manufacturers.
PQRs are not required for bulk liquefied gases.
PQRs are required for all compressed medicinal gases that are filled on-site.
"Medical air" needs to be included as part of the PQR if manufactured on-site by a batch wise production process (as per other compressed medicinal gases). Medical air is only subject to Part 1 of GMP and not subject to Part 2, due to the nature of its manufacture.
The requirement for conducting reviews of the stability monitoring programme will be exempt provided expiry dates are not put on the cylinder labels.
|1.5 and 1.6||
Quality risk management
New GMP section - relevant to gas manufacturers.
The new requirement for performing Risk Assessments is applicable to all TGA licensed manufacturers in Australia.
Annex 20 is voluntary. It provides useful guidance in the tools available for conducting Risk Assessments.
|3.2||Replaced by specific requirements in Annex 6: clause 3.1.2|
|3.3||Lighting should be adequate for the tasks being performed by the filling operators. Temperature is only relevant when calculating the settled pressure of the gas. Ventilation of the gas filling area must be adequate for safety reasons in the event of gas leakage. Humidity is not relevant to closed filling systems.|
|3.7||Applicable (replaced by specific requirements in Annex 6: clause 3.1.2 and 3.1.3).|
|3.26||Analysis for batch specific testing and for full cylinder analysis against the product specifications (i.e. BP/EP/USP monographs), should be performed using equipment that is appropriately calibrated, maintained and where applicable utilise validated systems.|
|4.14-4.15||On-site Medical Air production will be included in the TGA GMP inspection and that the control and quality of any bulk pharmaceutical product (BPP) manufactured on-site will be included in the scope of the TGA GMP inspection, but limited to the areas of quality control, transference, validation (including change control) and acceptance of the BPP prior to filling.|
|4.17||Batch processing records are applicable to all medicinal gases filled on site with specific details included in Annex 6, clauses 4.1 and 5.3.6.|
|4.18||The information to be entered in Batch Packaging Records is not applicable and is replaced by clause 4.1, Annex 6.|
|4.26||Environmental monitoring and pest control are not applicable.|
|4.29||Not required as equipment and areas are product specific.|
|5.12||Applicable to medicinal gas filling only.|
|5.18||Not applicable. Cross-contamination is prevented by specific requirements in Annex 6.|
|5.19||Not applicable. Cross-contamination is prevented by specific requirements in Annex 6, with the exception of clause 5.19(f) which is applicable to gas manufacturers.|
Starting materials in the storage area should be appropriately labelled (see chapter 5, item 13). Labels should bear at least the following information:
For medicinal gas manufacture, the term 'starting material' also refers to the empty gas cylinder.
|5.35-5.36||Applicable to mixed gas manufacturers only.|
|5.38-5.39||Applicable to mixed gas manufacturers only.|
|5.54||Replaced by on-line checks in Annex 6.|
|5.56||Applicable to printed batch code labels only.|
|5.57||Applicable to printed batch code labels only.|
|6.8||Under Section 20 of the Therapeutic Goods Regulations, licensed manufacturers must retain records at the licensed premises for at least 12 months after the expiry date of the goods or, if there is no expiry date, for not less than 6 years after completion of manufacture.|
|6.15||No analytical method validation is required provided current EP/BP/USP monographs are adhered to.|
|6.23-6.33||Not relevant to medicinal gas manufacturers unless expiry dates are specified on the gas cylinder label.|
|8.7||New requirement relevant to gas manufacture:- Special attention should be given to establishing whether a complaint was caused because of counterfeiting.|
|8.8||New requirement relevant to gas manufacture - The Competent Authorities should be informed if a manufacturer is considering action following possible faulty manufacture, product deterioration, detection of counterfeiting or any other serious quality problems with a product.|
|8.16||Relevant to gas manufacture - The effectiveness of the arrangements for recalls should be evaluated regularly.|
|2.1||This does not prevent a trained independent operator who meets the criteria from being authorised to perform release for supply of medicinal gases.|
|3.1.1||A "separate area" is usually achieved by filling medicinal gases on manifolds dedicated to medicinal gases. Such an area should have sufficient space around to perform all the filling related tasks.|
|5.1||Chapter 5: clauses 5.21-5.24 and annex 6: clause 5.1 are interrelated and therefore annex 6 clause 5.1 is applicable to medicinal gas manufacturers. Validation is also discussed in Annex 11 and 15.|
Clause 5.2.1: Bulk Gases produced outside the TGA licensed site and transported to the Gas manufacturer by tanker remain exempt from clause 5.2.1
Clause 5.2.2:- Applicable
Clauses 5.2.3-5.2.10: On-site Medical Air production will be included in the TGA GMP inspection and that the control and quality of any bulk pharmaceutical product (BPP) manufactured on-site will be included in the scope of the TGA GMP inspection, but limited to the areas of quality control, transference, validation (including change control) and acceptance of the BPP prior to filling
Clause 5.2.11:- This clause is relevant to all Gas manufacturers who receive bulk tanker deliveries
A recorded check to determine that the cylinder has a positive pressure which is demonstrated to be sufficient to ensure that the cylinder is not emptied will be required.
|5.3.7||The stated maximum impurity level of 500ppm v/v will be understood to have been achieved by the required pre-fill cylinder preparation. Evidence that it is being achieved will not be required.|
Gas cylinders have traditionally not been stored under cover and as this is not known to have caused any adverse effects, it continues to be acceptable provided that:
Gas cylinders have traditionally been transported in open vehicles. This is acceptable provided that: