EXPLANATORY STATEMENT

Agricultural and Veterinary Chemicals Instrument No. 1

(Manufacturing Principles) 2007

Subsection 23(1) of the Agricultural and Veterinary Chemicals Act 1994 provides that the Australian Pesticides and Veterinary Medicines Authority (APVMA) may determine for the purposes of Part 8 of the Agricultural and Veterinary Chemicals Code (the Agvet Code) scheduled to the Agricultural and Veterinary Chemicals Code Act 1994 written principles to be observed in the manufacture of chemical products that are consistent with the Agvet Code, the Agricultural and Veterinary Chemicals Code Regulations 1995 and the laws of any jurisdiction that relate to occupational health or safety.

Subsection 32(1) of the Agricultural and Veterinary Chemicals (Administration) Act 1992 provides that the Chief Executive Officer of the APVMA may exercise any of the powers and functions of the APVMA.

The Commonwealth and all States and Territories have agreed to a National Registration Scheme for Agricultural and Veterinary Chemicals.  The National Scheme sets out the regulatory framework for the management of pesticides and veterinary medicines in Australia by a single agency.  The APVMA is the current name for the National Registration Authority for Agricultural and Veterinary Chemicals (NRA) established in 1993 as an independent statutory authority responsible for the Commonwealth’s regulatory functions under the Scheme.

The National Registration Scheme also provides for a national, uniform and cooperative legislative regime throughout Australia administered by the APVMA.  The centrepiece of the legislation is the Agvet Code, which has been applied to all Australian states and territories – the ‘participating territories’.  Under the Agvet Code, the APVMA is responsible for the registration, quality assurance and compliance of pesticides and veterinary medicines up to and including the point of retail sale in Australia. 

Part 8 of the Agvet Code provides for the licensing of manufacturers of veterinary medicines by the APVMA, where the manufacturer complies with the APVMA’s manufacturing principles. 

The APVMA has determined new Manufacturing Principles, which have been collated from an Australian Code of Good Manufacturing Practice for Veterinary Chemical Products published by the APVMA on 29 March 2007.  These new Manufacturing Principles are to replace the existing Principles determined by the then NRA on 14 April 1997.  The 1997 Principles are being repealed.

The new Manufacturing Principles have been written specifically to meet the needs of all Australian veterinary chemical manufacturers.  A Working Group was formed in August 2003 comprising APVMA, peak industry representatives, and a number of licensed veterinary manufacturers.  The Working Group met regularly for two years.  Drafts of the proposed revised Manufacturing Principles and the Code of GMP were released to nearly all manufacturers and other interested parties for comment in May 2005.  In August 2005 a draft Regulation Impact Statement (RIS) was released for broad community consultation.  Nearly all comments received have been reflected in the final versions of the Manufacturing Principles and the Code for GMP.  A final RIS was released in September 2005 detailing the comments received, the changes made to reflect those comments, and the few comments that were not accepted with the reasons for non-acceptance.  A copy of the final RIS is included in this explanatory statement.

The new Manufacturing Principles and the Code of GMP are consistent with state and territory laws relating to occupational health and safety.

The Agricultural and Veterinary Chemicals Instrument No. 1 (Manufacturing Principles) 2007 is a legislative instrument for the purposes of the Legislative Instruments Act 2003.

NOTES TO ITEMS

Item 1 Name of Instrument

1. This item states that the full name of the Instrument is the Agricultural and Veterinary Chemicals Instrument No. 1 (Manufacturing Principles) 2007.

Item 2 Commencement

2. This item provides that the Instrument will commence on 1 May 2007.

Item 3 Determination of Manufacturing Principles

3. This item determines that, pursuant to subsection 23(1) of the Agricultural and Veterinary Chemicals Act 1994, for the purposes of Part 8 of the Agricultural and Veterinary Chemicals Code (the Agvet Code), the written principles to be observed in the manufacture of veterinary chemical products are as prescribed in the Schedule to the Instrument.  These new Manufacturing Principles are being determined by the APVMA to replace the original Principles made in 1997. 

Schedule—Manufacturing Principles for
Veterinary Chemical Products

Item 1 Interpretation

1. The first sub-item clarifies that expressions used in the Instrument have the same meaning as in the Agvet Code or the Agvet Regulations.

2. The other sub-item provides a definition for several words such as the Code of Good Manufacturing Practice and the Act.  The technical term specified biological process (used in item 15) is defined broadly and the term manufacture is defined very widely so as to include all possible steps in the process of manufacture.

Item 2 Compliance with Code of Good Manufacturing Practice

3. This item makes it a requirement that, subject to these Principles, veterinary chemical products must be manufactured in compliance with the APVMA’s Australian Code of Good Manufacturing Practice for Veterinary Chemical Products as in force on 29 March 2007.

Item 3 Quality Management

4. Sub-item (1) requires manufacturers of veterinary chemical products to have a quality assurance system in place that ensures products proposed for supply and sale are fit for their intended use, comply with registration requirements and do not place treated animals or users at risk due to inadequate quality, safety or efficacy.

5. Sub-item (2) clearly details five broad matters that the quality assurance system required by sub-item (1) must ensure.

6. Sub-item (3) details four additional requirements of the quality assurance system required by sub-item (1).  The quality assurance system must be relevant to the nature and intended use of the product; fully documented; monitored for effectiveness; and provide for continuous improvement.

Item 4 Personnel and Training

7. Sub-item (1) requires that veterinary chemical products must be manufactured under the management and supervision of appropriately qualified, trained or experienced persons who understand the specialised technical, quality and legal requirements relating to the manufacture of veterinary chemical products for which they have responsibility.  Persons involved in the manufacture of veterinary chemical products must also have their duties and responsibilities clearly defined by the manufacturer.

8. Sub-item (2) details training competencies required of manufacturing staff.

9. Sub-item (3) addresses resource requirements for the manufacture of veterinary chemical products.

Item 5 Buildings and Grounds

10. Sub-item (1) details a number of requirements in relation to the location, design, construction, maintenance, and utilisation of buildings in which veterinary chemical products are manufactured.

11. Sub-item (2) sets out several further requirements in relation to the manufacturing environment for veterinary chemical products

Item 6 Equipment

12. Sub-item (1) provides that equipment used in the manufacture of veterinary chemical products must be suitable for its intended purpose and appropriately operated, maintained and cleaned.  Additionally, equipment must be correctly installed and operated in accordance with written instructions that are appropriate for the equipment.

13. Sub-item (2) provides that the design and layout of equipment must be such that the risk of manufacturing error is minimised and that effective cleaning and maintenance are possible in order to avoid any adverse environmental effect on the quality of the product.

Item 7 Documentation

14. This item provides that manufacturers must establish and maintain a comprehensive system of documentation that provides precise specifications for starting materials, intermediate materials and finished products; manufacturing formulae and instructions; and operating procedures for manufacturing and quality control activities.  For each veterinary chemical product produced, this system of documentation must also provide a complete history of each item, batch, or quantity manufactured in a specified timeframe at the premises and establish a traceable connection between raw materials and the finished product.

Item 8 Computer Systems

15. Sub-item (1) provides that where, in any step of manufacture, a computer is used for any activity that may affect the quality, safety or efficacy of a product, then the computer system must be subject to the principles of quality system management to ensure operational suitability.

16. Sub-item (2) provides that the introduction of computer systems into any manufacturing process must not adversely affect product quality or quality assurance.

Item 9 Production

17. Sub-item (1) provides that veterinary chemical products must be manufactured to specifications in accordance with manufacturing information supplied as part of the application for registration of the product, including any further manufacturing information supplied as part of a subsequently granted application for variation of registration of the product.

18. Sub-item (2) requires production operations to follow documented procedures that have been clearly defined by the manufacturer.

19. Sub-item (3) requires any critical manufacturing process and any change to that manufacturing process to be validated and formally approved by an authorised person.  Where a change in the manufacturing process affects the registered specifications of the finished product, formal approval of such changes must be obtained from the registering authority before the affected product is released for supply

Item 10 Quality Control

20. Sub-item (1) requires manufacturers of veterinary chemical products to have in place an effective quality control system that is designed to ensure that, before products are released from manufacture for supply, they meet registered specifications and have been manufactured in accordance with the manufacturer’s documented procedures.

21. Sub-item (2) requires the person responsible for quality control to be independent of other aspects of the manufacturing operation to such an extent as to allow effective implementation of the quality control function.

22. Sub-item (3) provides that manufacturers must ensure that analytical laboratories and animal testing facilities used in a step of manufacture follow the principles of good laboratory practice.

Item 11 Contract Manufacture

23. In circumstances where all or part of the manufacture of a veterinary chemical product is contracted to another party, this sub-item requires the licensed manufacturer to ensure that, before manufacture commences, all parties have signed a written ‘GMP Agreement’ that clearly specifies each party’s responsibility in relation to every aspect of the manufacturing process, assurance of product quality and consistency with product registration particulars.

24. Sub-item (2) provides that arrangements for contracted steps of manufacture must not compromise the quality of the product.

25. Where a contractor is authorised to manufacture under the licence of another manufacturer, sub-item (3) requires the licence holder to exert direct control and oversight of the quality management of the contracted step.

Item 12 Internal Audits

26. This item provides that manufacturers of veterinary chemical products must regularly and systematically carry out internal audits of all aspects of their manufacturing operations, as well as of their quality assurance program, in order to monitor compliance with their authorised procedures, standards and requirements and to ensure product quality.  Steps must be taken to implement any necessary corrective and preventive action identified by those internal audits and to assess the outcomes.

Item 13 Complaints and Product Recalls

27. Sub-item (1) requires manufacturers of veterinary chemical products to have in place a system of handling complaints regarding products they have manufactured or otherwise handled on the licensed premises.  There must be a documented system of recording, investigating and, where appropriate, acting upon all complaints that may be related to product quality.

28. Sub-item (2) further requires manufacturers to have in place a documented and effective procedure for recalling from the marketplace product that is known to be defective, or is suspected of being defective.

Item 14 Sterile Products

29. Sub-item (1) provides that veterinary chemical products that are required to be, or are represented as being, sterile must be manufactured in separate, controlled areas in the premises that have high standards of hygiene.  The separate area must also have a system of controlling particulate contaminants that is appropriate to the class of veterinary chemical product being manufactured. 

30. Sterile products must additionally be manufactured with special care and attention to detail and in accordance with procedures established and validated by the manufacturer.

31. Sub-item (2) provides that the manufacturer must establish procedures and have equipment available (or in the case of bioburden, have access to equipment) to adequately monitor               the microbiological status of the environment in production areas; and the microbiological burden of the veterinary chemical products that are to be sterilized.

Item 15 Immunobiologicals and Other Products of Biological Origin

32. This item provides that veterinary immunobiological products and other chemical products of biological origin, including those that are manufactured using a specified biological process, must be manufactured using biological starting materials that are, or are derived from, biological materials demonstrated to be as free as practicable from adventitious contamination. 

33. These products must also be manufactured in premises that are designed, constructed and maintained so as to provide an appropriate level of containment of the biological or microbiological agents being handled and to permit effective decontamination from these agents or from toxic residues by procedures that are established and validated by the manufacturer and maintain the safety of personnel.

34. In cases where uniformity of product depends on deriving batches from a seed lot, veterinary immunobiological products and other chemical products of biological origin must be manufactured by maintaining the lots in secure and protective storage and by keeping meticulous records of their origin and disposition.

Final Regulation Impact Statement

Revision Of Manufacturing Principles and the Australian Code Of Good Manufacturing Practice for Veterinary Chemical Products

Background

The APVMA is the independent Australian government authority responsible for the assessment and registration of pesticides and veterinary medicines. Veterinary medicines include all veterinary chemical products such as vaccines, antibiotics, worming treatments, flea and tick washes and other parasiticides, for use on domestic animals and animals for production.

As a Commonwealth statutory authority, the APVMA operates in accordance with governing legislation. The principal responsibilities of the APVMA are described in the Agricultural Chemical (Administration) Act 1992 and the Agricultural and Veterinary Chemicals Code Act 1994 (Agvet Codes).

In accordance with these Agvet Codes, the APVMA must be satisfied that veterinary chemical products are of a high quality; do not pose a threat to people, animals, crops, plants, things or the environment; will not pose an unacceptable risk to trade; and will work effectively.

The APVMA expects that all veterinary chemical products supplied in Australia are manufactured in accordance with the APVMA’s Manufacturing Principles and associated codes of Good Manufacturing Practice (GMP).  GMP is a system for ensuring that quality is built into products during manufacture rather than placing sole reliance on testing prior to release. It is designed to minimise the risk of foreseeable errors and process failures so that veterinary chemical products consistently comply with their approved registered particulars.

Australian manufacturers of veterinary chemical products need to be licensed by the APVMA under Part 8 of the Agvet Codes.  Australian manufacturers undergo regular audits, normally at intervals of 18 - 24 months, to ensure their continued compliance with the APVMA’s Manufacturing Principles and the relevant Code of Good Manufacturing Practice (GMP).  The current Manufacturing Principles came into force on 14 April 1997, while the Australian Code of Good Manufacturing Practice for Veterinary Preparations and the Australian Code of GMP for Homemixed Feeds, Feed-milling Industry and Stock-feed Premixes were first published by the Standing Committee on Agriculture in 1992.

In 2001 a survey was conducted to determine the industry standpoint on various GMP-related issues.  The feedback received from this survey showed interest in harmonisation with leading international codes.  In 2003 the APVMA resolved that the Manufacturing Principles and the Codes should be revised in line with broader international GMP requirements.  A Working Group, formed in August 2003 with representatives from industry and the APVMA, met regularly during the intervening 24 months.  A first draft of the revised Manufacturing Principles and the Code of Good Manufacturing Practice for Veterinary Medicines was provided to all APVMA-licensed manufacturers and APVMA-authorised auditors in May 2005 for comment.  A Consultation (draft) Regulation Impact Statement, reviewed by the Office of Regulation Review, was released for public comment in August 2005.

Part 1: Issues

Part 8 of the Agricultural and Veterinary Chemicals Code Act 1994 (http://www.apvma.gov.au/about_us/AgrVetChemCode94.rtf) mandates the licensing of manufacturers of veterinary chemical products.  In Part 8 it is stated that:

'A licensee is required ... to comply with manufacturing principles determined by the APVMA, which may include codes of good manufacturing practice'.

The current Manufacturing Principles came into force on 14 April 1997, while the Australian Code of Good Manufacturing Practice for Veterinary Preparations and the Australian Code of GMP for Homemixed Feeds, Feed-milling Industry and Stock-feed Premixes were first published by the Standing Committee on Agriculture in 1992.

Australian manufacturers are currently audited for compliance with these principles and the codes that have been in place since the APVMA’s licensing scheme was introduced and their review is timely. 

The current Manufacturing Principles and Codes have not been revised since their introduction. Veterinary chemical manufacturers have expressed concern that the Codes are not clear in differentiating between a requirement and a guidance, do not address manufacturing details for all veterinary chemical products and may be interpreted in different ways by manufacturers and auditors. Further, veterinary chemical manufacturers identified that they may need to comply with multiple codes of manufacture depending on the product manufactured or the requirements of international regulators.

To address these problems with the current documents the APVMA is currently reviewing the Manufacturing Principles and associated codes of good manufacturing practice. This was to ensure these standards reflected contemporary good practice and were sufficiently clear to allow licensed manufacturers to comply.

Issue 1 – Need for clarity and transparency in APVMA requirements

Members of the veterinary chemical product manufacturing industry have expressed concern over the lack of clarity and transparency in APVMA requirements for manufacture of veterinary chemical products. Lack of clarity may lead to industry behaviour that is not compliant with contemporary good manufacturing practice. This can subsequently lead to sub-standard veterinary product quality that may pose risks to animal and human health and safety.

In following the principles of good manufacturing practice, manufacturers need clear separation between APVMA requirements and guidance. The Manufacturing Principles should be interpreted as performance-based standards whereas a supporting document such as a Code of Practice should be interpreted as a guidance that includes more prescriptive details. Currently, there is no direct relationship between the mandatory, performance-based standards in the Manufacturing Principles and the essentially guidance material provided in the Codes of GMP.  It is therefore unclear as to what needs to be done to satisfy the requirements of the Manufacturing Principles whilst using the guidance of the Codes. The lack of a direct relationship causes manufacturer and auditor confusion and uncertainty in day-to-day interpretation of the documents. Improving the relationship between the Manufacturing Principles and the Code, whilst somewhat machinery in nature, should facilitate greater understanding of both documents.

In addition, the current Codes of GMP contain both ‘musts’ and ‘shoulds’ and the relative weighting of these requirements is unclear.  An example of the lack of clarity is clause 61 (5) of the Agvet Code Regulations that requires that samples for products without an expiry date “must” be retained for at least 6 years after the date of manufacture, while the Clause 8.6 of the Australian Code of Good Manufacturing Practice for Veterinary Preparations indicates that such retention samples “should” be held for 12 months after it would be reasonable to expect all of the batch to be sold to consumers. Consideration of these issues is important in review of the Codes.

Furthermore, the Manufacturing Principles and the Codes are silent in some critical aspects of manufacture.  For example, clause A1.1 states that “The prevention of cross-contamination is of paramount importance.  As a general principle, only comparable groups of micro-organisms must be processed in an area at any one time, and all culturing processes must be segregated from “clean” areas”.  However, the Code provides no guidance as to the prescriptive standards of buildings, plant and equipment that apply to “clean” areas required for aseptic processing.  The interpretation and enforcement of many Code requirements is therefore subjective.

This lack of prescriptive guidance detracts from the utility of the current Codes and may lead to exposure of consumers and animals to possible health and safety risks associated with quality defects in veterinary medicines.

Issue 2 – Range of Veterinary Chemical Products covered by GMP

While the need for government regulation of veterinary medicines or veterinary chemical products is accepted internationally, the legal definitions of these terms and the strategies for enforcement differ between countries.  For example, in the United States, veterinary medicines are regulated by various agencies, depending on the nature of the veterinary medicine.  In Australia, the legislative definition of a veterinary chemical product is fairly broad and includes some lower risk products (such as probiotics) that must be manufactured under good manufacturing practice in Australia, but are not regulated by some other foreign regulators.

The APVMA needs to provide adequate guidance for the full range of chemicals that need, under the legislation, to be manufactured in compliance with GMP. Although the current Codes provide guidance on the manufacture of certain product types, there are a number of products and facilities that are not specifically covered under the current codes of GMP.  Examples of these include products such as therapeutic pet foods and facilities such as analytical laboratories.  Determining whether such facilities are compliant with broader APVMA requirements is difficult and may lead to different interpretations by manufacturers and auditors.

There also needs to be recognition that consumer expectations for product quality differ across the range of veterinary chemical products and that these differences in expectations should be reflected in the manufacturing standards and requirements that apply to specific product types.  For example, consumers expect that injectable and highly potent veterinary medicines, such as vaccines, anaesthetics and steroids, will conform to the highest pharmaceutical standards.  However those same expectations do not apply to lower risk products such as bloat oils (that are sprayed onto pasture) and salt blocks (that are left exposed in paddocks for long periods of time).  With some other veterinary chemical products the correct dosage is critical, while it is not with others that are consumed ad libitum.  As a consequence, requirements in Manufacturing Principles and guidance in the codes need to provide for essential principles that apply to all veterinary chemical products as well as flexibility related to certain types of product being manufactured.

Issue 3 – Manufacturer compliance with multiple codes and the need for greater harmonisation.

A significant proportion of Australian manufacturers need to comply with more than one code of GMP.  Currently, the Therapeutic Goods Administration accredits more than 30% of APVMA-licensed manufacturers as they manufacture both human and veterinary medicinal products.  Such manufacturers need to comply with both the Australian Code Of Good Manufacturing Practice For Medicinal Products as well as the Australian Code of Good Manufacturing Practice for Veterinary Preparations.  The former code is based on the PIC/S Guide To Good Manufacturing Practice For Medicinal Products.  In addition, some veterinary chemical product manufacturers looking to export products need to comply with the requirements of the importing country while others with a multinational corporate structure need to comply with corporate standards that are commonly based on GMP requirements in Europe or the USA.  Differences between codes increase the costs of compliance without providing any compensatory benefit to either consumers or manufacturers.  Code differences may disadvantage local manufacturers, effectively precluding small manufacturers from participating in export related opportunities. 

Part 2:  Objectives

The following objectives were developed against which current or new manufacturing standards are assessed.

Objective 1 – Clarity and scope of APVMA requirements

The APVMA’s manufacturing standards should be clearly stated to enable Australian manufacturers of veterinary chemical products to comply with the standards.  The scope of these standards should also cover the range of products and steps of manufacture to be regulated. 

Objective 2 – Alignment with domestic and international codes

The APVMA’s manufacturing standards should be more closely aligned with other domestic and international codes of GMP in order to:

• increase consumer confidence that all veterinary chemical products in the Australian marketplace are manufactured to a similar standard regardless of  whether they were manufactured locally or overseas;
• improve manufacturing efficiency associated with reduced regulatory complexity;
• facilitate export opportunities for local manufacturers as the APVMA’s manufacturing standards progressively gain recognition as being “equivalent” with those of major international trading partners.

Part 3: Identification of Options

The purpose of this Regulation Impact Statement is to identify and consider the various options related to standards for veterinary chemical product manufacture.   Due to the legislative basis for a Manufacturing Licensing Scheme for veterinary chemical products and due to the critical nature of these products, options for the abolition of manufacturing standards were not considered to be feasible in light of the potential risks to animal and public health and safety.  Similarly, the development of highly prescriptive, detailed requirements covering all types of products and methods of manufacture was not considered to be feasible due to both the scale of the task and the ever-changing nature of technological development.  The three options considered in more detail generally involve the utilisation of mandatory performance-based standards (such as the currently Manufacturing Principles) and supporting guidelines (such as are in the current Codes).

Option 1 – Maintain the status quo and retain the current APVMA Manufacturing Principles and associated Codes of GMP

A decision to maintain the status quo and retain the current Manufacturing Principles and two associated codes of GMP will not satisfy the two objectives (clarity and international alignment), outlined in Part 2.  The shortcomings outlined in Part 1 would not be addressed.  Performance based requirements in the existing Manufacturing Principles would contain “gaps” while the Codes would remain silent on certain types of manufacturing operations.  Some guidance would remain unclear while other requirements would not reflect the underlying legislation.  In addition, a significant proportion of manufacturers would continue to need to comply with multiple codes of GMP.  Auditing against, and enforcement of, the APVMA’s manufacturing standards will remain difficult and there is a risk that consumers may perceive locally made products as being of inferior quality to those that are imported.  The APVMA does not consider this option, retention of the current APVMA Manufacturing Principles and associated Codes of GMP, to be viable.

Option 2 – Adopt the PIC/S Guide to Good Manufacturing Practice for Medicinal Products

Adoption of the PIC/S Guide to Good Manufacturing Practice for Medicinal Products would ensure a degree of harmonization with the manufacturing standards that apply in Europe, largely satisfying the second objective.  However, as the PIC/S Guide to Good Manufacturing Practice for Medicinal Products was primarily targeted towards the human pharmaceutical industry, these manufacturing standards should not be applied directly to manufacture of some veterinary chemical products, such as probiotics and therapeutic pet foods.  In Europe these products are covered by other requirements.  Predictably, this option was vigorously opposed by some sectors within the Australian veterinary manufacturing industry that argued that some PIC/S requirements were too prescriptive and were not appropriate for our industry.  As an example, there are proportionately more small manufacturers (“owner/operators”) in Australia than in Europe and the PIC/S Guide to Good Manufacturing Practice for Medicinal Products does not provide sufficient flexibility for these small manufacturers.  For example, PIC/S clause 2.2 requires that “The manufacturer must have an organisation chart” and PIC/S clause 2.3 requires that “The heads of Production and Quality Control must be independent from each other”.  Complying with these requirements may not be possible for some small Australian manufacturers.

In considering the objectives identified in Part 2, adoption of the PIC/S guide also provides clarity, but would not provide appropriate manufacturing guidance for the range of veterinary chemical products on the Australian market. As a consequence of these issues, APVMA does not consider this option, the adoption of the PIC/S Guide to Good Manufacturing Practice for Medicinal Products, to be feasible.

Option 3 – Revise the current APVMA Manufacturing Principles and associated Code(s) of GMP and adopt these revised standards

Under this option, the Manufacturing Principles and associated code(s) would be revised to bring them into closer alignment with major international codes, including the PIC/S Guide to Good Manufacturing Practice for Medicinal Products.  In addition, the revised requirements would need to incorporate a degree of flexibility and discretion in order to deal with the range of products manufactured by veterinary chemical product manufacturers licensed by the APVMA.  The APVMA intends to seek international recognition for the revised Manufacturing Principles and the code, acknowledging that “equivalence” does not mean “identical”.  Revisions would need to clarify requirements and guidance and provide better information on the expectations of the APVMA regarding compliance with the Manufacturing Principles and associated Code(s) of GMP. The APVMA views this as the most viable option.

A revised Manufacturing Principles and Australian Code of Good Manufacturing Practice for Veterinary Chemical Products are attached to this Final Regulation Impact Statement. The revisions have been drafted in consultation with the veterinary chemical industry, as outlined under Part 5.

Part 4: Assessment of the Costs and Benefits of the Preferred Option, Option 3

Impact Group Identification

The three main groups impacted by Option 3 are the community including the rural sector, the chemical industry and the APVMA. The community and the rural sector are the consumers of veterinary chemical products, for use on domestic and production animals.  The chemical industry refers to the manufacturers and registrants of veterinary chemical products that are manufactured in Australia and/or overseas.  The APVMA is the government statutory authority responsible for regulating veterinary chemical products.

Benefits to the community and the rural sector

The major benefit to consumers will be increased assurance in the safety and quality of veterinary chemical products.  By aligning the revised requirements with those in leading international codes, veterinary chemical products will be manufactured using quality standards that represent best international manufacturing practice.  It is not possible to quantify this effect.  In some instances, the benefits may be relatively minor as many of the proposed requirements are implied “industry standards”.  However, by strengthening some quality assurance requirements, community benefit may be derived from a reduction in the rate of product quality defects and product recalls.  While such occurrences may be relatively infrequent, their cost can be significant.

Costs to the community and the rural sector

The community and rural sectors may experience an increase in the price of some veterinary chemical products as some manufacturers may need to pass on costs associated with process change to comply with the revised requirements.  The APVMA it is not able to predict whether this may occur, or to what degree it may occur, and we do not have quantitative information on such costs. However, the APVMA has endeavoured to keep such costs to a minimum by working with industry representatives to ensure that guidance in the revised Code of GMP is practical and cost-effective. 

Despite public consultation, the APVMA did not receive submissions or further information on such costs.

Benefits to the APVMA

The provision of more detailed guidance in the revised Manufacturing Principles and associated Code of GMP will provide the APVMA with greater confidence that its requirements are understood by industry, that all veterinary chemical products manufactured locally are manufactured in compliance with APVMA requirements, and that these requirements reflect international best practice.  Greater clarity and transparency will enable the APVMA to more easily enforce compliance with manufacturing standards, where this becomes necessary.

Costs to the APVMA

The costs to the APVMA will include publication of the new documents, development of auditing documents and provision of industry and auditor training on the new standards.  The APVMA estimates these costs to be up to $50,000.

Benefits to industry

The major benefit to industry will be the provision of clear requirements and guidelines that can be readily interpreted by both manufacturers and auditors.  The provision of more detailed guidance and direct relationship between the performance standards in the Manufacturing Principles and the guidance in the Code should increase the general utility of these standards, reducing the need for new manufacturers to engage regulatory consultants.  As the revised requirements also align with those of other leading regulators, including the Therapeutics Goods Administration, there should also be benefits associated with reduced regulatory complexity and facilitation of export.

Costs to industry

The veterinary manufacturing industry already has costs associated with maintenance of licensing under the current Manufacturing Licensing Scheme arrangements, including on-going quality assurance and quality control systems to satisfy APVMA auditors of compliance with good manufacturing practice.  We anticipate that Option 3, revision of the existing Manufacturing Principles and Codes of Good Manufacturing Practice, will result in minimal additional overall costs to the Australian veterinary chemical product manufacturing industry.  The revised Code takes contemporary industrial practices into consideration and provides better information on standards relevant to particular product types.  There may be additional costs to industry in satisfying some quality assurance aspects of the revised standards such as process validation.  However, the revised standards limit such requirements for validation to crucial steps such as cleaning and process residue validations.  Some smaller operations may need to strengthen certain quality assurance aspects of their manufacturing operation in order to comply with the new requirements.  Here it is argued that the imposition of such costs is justified in the interests of product quality and public safety.

Costs of complying with the revised Code are expected to be partially off-set by savings associated with simplified and standardised quality systems and possible reductions in defective products due to greater emphasis on quality assurance activities. 

Despite public consultation, the APVMA did not receive submissions or further information on such costs.

Table 1. Summary of costs and benefits to the community, rural sector, industry and APVMA and Government.

Part 5: Consultation

The APVMA recognised industry perception that international Codes of GMP were stricter and less flexible than the current Australian codes and that consideration of changes to the Australian codes would need genuine and detailed consultation with industry.  Expressions of interest to form a group to consider Manufacturing Principles and Code revisions were invited from all APVMA-licensed manufacturers and a Working Group was formed in August 2003, comprising representatives from the APVMA, Avcare (a national chemical industry association), Veterinary Manufacturers and Distributors Association, a manufacturer and 2 other interested persons.  The Working Group met regularly for 2 years.  Whilst this intense consultative process was somewhat prolonged, ‘up-front’ industry participation has been of benefit to the production of the revised Manufacturing Principles and associated Code that can be applied to contemporary manufacturing practice.

To further ensure industry participation, and to maximise the benefits of the public consultation, drafts of the revised Manufacturing Principles and the Code of GMP for Veterinary Chemical Products were provided to over 230 manufacturers and APVMA-authorised auditors for comment in May 2005.  This was followed by a release of the release of the (draft) consultative Regulation Impact Statement on the APVMA website in August 2005 for broad community consultation.  During this latter phase, the Authority actively sought comments on the costs and benefits of the proposed changes to the community and rural sector as well as to industry. 

In total, feedback was received from a total of 12 respondents.

Overall comments were supportive and included:

• “Good job”
• “The new Australian code is a huge improvement on the previous code … and brings GMP requirements into par with international manufacturing standards”
• “Thank you for the opportunity to review this very important document.  We would like to convey from the outset, that this new code of GMP is a thoroughly detailed and workable document and is a credit to all those dedicated people who have input into its creation, structure and/or content”
• “Overall the revised code is much better than previously as it does provide more flexibility by the use of the word “should” rather than “must”, and we trust the above comments are useful”.

Many comments were directed towards the more technical aspects of the Code.  The Working Group considered all submissions and consequential changes were made, including:

• Deletion of the words “where applicable” from the clause relating to the provision of alarms for temperature controlled storage areas (317).
• Clause 332 was modified to more clearly differentiate between the use of wood-based material for construction and support of equipment and its use in pallets.
• “Hygienic” was added to describe hand-drying facilities (344).
• The guidelines for a Water Quality Manual (clause 752) were broadened to allow for inclusion of this document in the manufacturer’s Quality Manual.
• The requirement to follow “recognised good laboratory practices” (MP 23) was changed to “follow the principles of good laboratory practices” and these are outlined in clause 804.
• Air quality requirements for clean rooms (A1-021) were brought into line with current version of the PIC/S Code.
• An element of flexibility was introduced into the guidance on particle counting (A1-021 [a]) in response to a request from one dual manufacturer that the requirements for particle counting be applied to certain operations.  The change is consistent with the understanding that the TGA are likely to provide some exemptions when these requirements are brought in for TGA-licensed manufacturers.
• Guidelines for environmental monitoring (A1-031) were eased.

In a few cases where comments were not accepted, the submitters appeared to have underestimated the inherent flexibility within the Code, through the interpretation of “should”.  The Working Group resisted a request to define “small operation”, preferring to avoid being too prescriptive.  No details were received on the costs of the proposed changes to industry, or the community, including the rural sector.  The Working Group has also agreed to the proposed implementation timetable.

Part 6: Conclusion and Recommended Option

The preferred option

The APVMA’s preferred option is to adopt the revised Manufacturing Principles and the associated Code of Good Manufacturing Practice for Veterinary Chemical Products.  The date for implementation is given below.

Reasons for preferring this option

This option is preferred because it addresses the key objectives of clarity and transparency, alignment with international requirements and covers the range of veterinary chemical products and their manufacturers.  The option of retaining current Manufacturing Principles and Codes of GMP is not considered feasible as members of the veterinary chemical product manufacturing industry have expressed concern over the lack of clarity and transparency in these documents. The option of adopting the PIC/S Guide to Good Manufacturing Practice for Medicinal Products was also not considered feasible as it is a guide for human medicines and does not address manufacturing practices appropriate to the range of veterinary chemical products regulated by the APVMA or the range of facilities licensed by the APVMA.

The proposed revised Manufacturing Principles are the requirements that the APVMA expects manufacturers of veterinary chemical products to follow. The proposed revised Code of GMP provides guidance on meeting the requirements set out in the Manufacturing Principles. There is a clear relationship between the Manufacturing Principles and sections of the Code.  The Code also includes annexes dealing with specific product types.

Based on the positive feedback already received from Australian manufacturers of veterinary chemical products, we expect that the majority of Australian manufacturers will welcome the revisions. 

Part 7: Implementation and Review

Timetable to implementation

The following timetable outlines the process that will be undertaken in preparation for auditing of manufacturers of veterinary chemical products against the revised Manufacturing Principles and associated Code of Good Manufacturing Practice in January 2007:

October 2005

Presentation of the revised Manufacturing Principles, Australian Code of Good Manufacturing Practice for Veterinary Chemical Products and final RIS to the APVMA Board for approval.

November –December 2005

Authorisation of the APVMA Manufacturing Principles and the Australian Code of Good Manufacturing Practice for Veterinary Chemical Products with an implementation date of January 2007.  Publication of a Gazette Notice advising all manufacturers of the proposed changes.  The Manufacturing Principles and the Code of Good Manufacturing Practice for Veterinary Chemical Products are disallowable instruments that will be tabled before both Houses of Parliament.

January-December 2006

Transitional period.  Preparation of Audit Checklists, training of auditors and manufacturers.

January 2007 Commencement of auditing of manufacturers against the new requirements.

Review of the preferred option

A review of the revised requirements will be considered by the APVMA upon request of industry or if there are significant changes in manufacturing methods. The APVMA has a regular series of industry liaison committee meetings with product registrants and veterinary chemical manufacturers and conducts meetings with individuals or other interest groups as the need arises. These meetings provide opportunities for the APVMA to determine if the preferred option needs amendment. The processes also provide opportunities for stakeholder groups to provide feedback to the APVMA on issues related to implementation of the proposed approach. The APVMA anticipates that a review of the revised requirements would commence not less than 5 years after implementation and that the need for, and objectives of, a review would be developed through these industry committee meetings.

For further information contact:

Dr Bruce Johnson

Australian Pesticides and Veterinary Medicines Authority

PO Box E240, Kingston ACT 2604

Fax: (02) 6271 6442

Email: bruce.johnson@apvma.gov.au

References

Manufacturing Principles.  Determination No. 1 of 1997, National Registration Authority for Agricultural and Veterinary Chemicals, 1997.

Australian Code of Good Manufacturing Practice for Veterinary Preparations.  Standing Committee on Agriculture, SCA Report No 41, 1992.

Australian Code of GMP for Homemixed Feeds, Feed-milling Industry and Stock-feed Premixes Standing Committee on Agriculture, SCA Report No 42, 1992.

Australian Code Of Good Manufacturing Practice For Medicinal Products, Therapeutic goods Administration, 1992.

Guide to Good Manufacturing Practice for Medicinal Products.  The Pharmaceutical Inspection Co-operation Scheme PE009-2, 2004.