EXPLANATORY STATEMENT
Subject - Therapeutic Goods Act 1989
Therapeutic Goods (Manufacturing Principles) Determination No 1 of 2009
The object of the Therapeutic Goods Act 1989 (the Act) is to establish and maintain a national system of controls for the quality, safety, efficacy and timely availability of therapeutic goods that are used in Australia or exported from Australia. The Therapeutic Goods Administration (the TGA) is responsible for administering the Act.
Section 36 of the Act empowers the Minister to determine, as required, principles to be observed by manufacturers of therapeutic goods relating, inter alia, to standards to be maintained, the procedures to be adopted and the manufacturing practices to be employed in the manufacture of such goods. Manufacturing Principles establish the minimum requirements to be observed for the manufacture of medicinal products for human use.
The purpose of the Therapeutic Goods (Manufacturing Principles) Determination No 1 of 2009 is to update manufacturing requirements set out in the Australian Code of Good Manufacturing Practice for Medicinal Products (2002) to reflect changes made to the Guide to Good Manufacturing Practice for Medicinal Products, (the PIC/S Guide), issued by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (jointly referred to as PIC/S). The PIC/S Guide is available at www.picscheme.org/publication.php?p=guides.
Changes made in the PIC/S Guide include the addition of technical requirements applying to the manufacture of active pharmaceutical ingredients, as set out in the Guidance for Good Manufacturing Practice for Active Pharmaceutical Ingredients (the ICH Guide). The ICH Guide is issued by the International Committee on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH was established for the purpose of making recommendations to improve harmonisation of technical guidelines. The ICH Guide is currently incorporated in the Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2002. This Manufacturing Principle will be revoked under this Determination No.1 of 2009. When the PIC/S Guide commences to operate on 1 July 2010 the ICH Guide will form a new Part of the PIC/S Guide.
The Determination will also revoke the Australian specific Code of GMP for Therapeutic Goods, Sunscreen Products (1994), as the compliance of sunscreen products can be assessed using the PIC/S Guide.
The Determination provides for a transitional period for manufacturers to make any changes to their manufacturing practices that may be needed to comply with the updated standards of Good Manufacturing Practice (GMP) which will become mandatory on 1 July 2010. Alternatively, manufacturers may elect to have the updated manufacturing standards apply at any time following the commencement of this Determination.
Most developed economies with equivalent regulatory requirements to those which apply in Australia adopt internationally harmonised regulatory standards for GMP. The PIC/S Guide has been adopted by the 37 member countries to the convention and/or co-operation scheme and accords with GMP standards used in the United States and New Zealand. Harmonisation with international standards facilitates a high degree of cooperation and exchange of information, and in some cases, has led to the establishment of Mutual Recognition Agreements (MRA) which minimise the regulatory burden on an increasingly globalised industry.
In practical terms, this permits the TGA to accept GMP certificates issued by a competent regulatory authority in a country with which Australia has a MRA, and to exchange confidential inspection reports, related non-public documents and information relating to non-compliance or product recalls. These actions significantly enhance the efficiency and effectiveness of the GMP inspection programs in both countries that are party to an MRA.
The Manufacturing Principles in Australia have been based on the PIC/S Guide since 2002, with only minor amendment since. An update to the Manufacturing Principles was planned as part of the establishment of a joint regulatory scheme for therapeutic product regulation with New Zealand, however, the two governments agreed to postpone implementation in July 2007. Therefore, this update will incorporate changes made to the PIC/S Guide that have been adopted internationally over the past six years. The update is necessary to maintain the equivalence of Australia’s regulatory scheme for the purposes of its MRAs with the European Community, Canada and Singapore.
The most significant changes in the update to the Manufacturing Principles relate to product quality reviews and sterility requirements. The product quality review will involve periodic assessment of previous reviews, in-process controls, failed batches, deviations and non-conformities, process or equipment changes, marketing authorisation variations, stability results, complaints and recalls, and technical agreements to identify improvements. The Annex for the manufacture of sterile medicinal products has made changes to particle count limits, the monitoring airflows in Grade A processing areas, protective clothing requirements, limits to aseptic process media fills and capping and crimping aseptically filled vials. Other changes being made through the adoption of the PIC/S Guide include more explicit requirements for monitoring product stability over the shelf life of a product.
The PIC/S Guide includes an informative (non-mandatory) Annex on the subject of Quality Risk Management. This Annex will not be a mandatory requirement of this Determination.
Under paragraph 6(d)(i) of the Legislative Instruments Act 2003 (LIA), an instrument is a legislative instrument for the purposes of section 5 of the LIA if it is declared to be a disallowable instrument under legislation in force before the commencement of the LIA. This Determination is a legislative instrument and is subject to tabling and disallowance in the Parliament under sections 38 and 42 of the LIA.
CONSULTATION
The TGA consulted on proposals to adopt the most current PIC/S Guide as the applicable medicines manufacturing principle for the proposed joint scheme for the regulation of therapeutic goods in Australia and New Zealand in 2006-07. A consultation paper was made available for public comment on the Internet and industry associations were invited to comment on the proposal. Following the postponement of the joint regulatory scheme by the respective governments in July 2007, the TGA has consulted with industry associations regarding the need to reflect updated international manufacturing standards in domestic legislation through this Determination.
The Deregulation Policy Division in the Department of Finance and Deregulation have been consulted and have not indicated any concerns with the proposed changes introduced by this Determination. The Office of Best Practice Regulation has also advised that a Regulatory Impact Statement is not required. (OBPR ref 10178).
This Determination is made by the delegate of the Minister for Health and Ageing in accordance with subsection 36(1) of the Act.
This Determination came into effect on the day after it was registered on the Federal Register of Legislative Instruments.
The details of this Determination are set out in Attachment A.
ATTACHMENT A
Section 1 provides that this Determination may be cited as the Therapeutic Goods (Manufacturing Principles) Determination No 1 of 2009.
Section 2 of this Determination provides that this Determination takes effect from the day it is registered on the Federal Register of Legislative Instruments.
Section 3 amends the Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2007 to remove requirements applicable to medicinal products, and revokes Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2002 .The amendments which will update the manufacturing standards set out in the Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2007, and the revocation of Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2002, do not commence to operate until 1 July 2010, therefore these Determinations will continue to apply until 30 June 2010 after which date the updated manufacturing standards become mandatory.
Section 4 is an interpretation provision and provides the definitions of terms and documents referred to in this Determination.
The PIC/S Guide includes three Annexes that are not applicable under this determination as they refer to human blood and plasma products, which are covered by other provisions under the Therapeutic Goods Act, 1989, or are veterinary products. This Determination interprets the Code as the subset of the PIC/S Guide that excludes these three Annexes.
Section 5 provides that the manufacturing principles set out in the Determination apply to manufacturers of medicinal products, active pharmaceutical ingredients and sunscreen products, but exclude manufacturers of blood and blood components, plasma and haematopoietic progenitor cells, human tissues and therapeutic devices.
Section 5 requires a manufacturer of therapeutic goods coming within the scope of the Determination to comply with the Code. Where the Code provides that a procedure or requirement ‘should’ be followed, manufacturers in Australia ‘must’ follow the procedure or requirement in order to comply with the Code.
Section 5 also sets out provisions for non-compliance with the Code. A failure to follow a procedure or requirement specified in an applicable Part of, or Annex to, the Code, will constitute a failure to comply with the Code, unless a manufacturer is able to demonstrate that its failure to follow a procedure or requirement, or an alternate procedure:
- will not increase the risk of harm or injury to any person or potentially have the effect of causing or contributing to such harm; and
- will not increase the risk of the therapeutic goods in question failing to comply with applicable standards and/or registration or listing requirements; and
- will not compromise the record keeping requirements contained in the Code.
Section 6 sets out transitional provisions between the commencement date of this Determination and the mandatory date of commencement of the updated manufacturing standards reflected in the Code on 1 July 2010. The transitional provisions will mean that:
- a manufacturer of a medicinal product, including a sunscreen, must comply with either Section 5 of this Determination or the Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2007; and
- a manufacturer of an active pharmaceutical ingredient must comply with either Section 5 of this Determination or the Therapeutic Goods (Manufacturing Principles) Determination No.1 of 2002.