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NOTE: This is an archived issue. The current issue of AgVetLink can be found at http://www.nzfsa.govt.nz/acvm/publications/agvetlink/
Standards Submissions |
Submissions were received on the following documents:
ACVM - Registration Information Requirements
ACVM - Registration Standard and Guideline for Chemistry
ACVM - Registration Standard and Guideline for Manufacturing
ACVM - Registration Standard and Guideline for Target Animal Safety
ACVM - Registration Standard and Guideline for Bioequivalence
ACVM - Registration Standard for Good Research Practices
ACVM - Registration Standard and Guideline for Efficacy of Anticoccidials in Poultry
An executive summary of these submissions is given in this supplement. An expanded report will be forwarded to submitters in late June/early July. Copies of this report will be available on the ACVM Group's website (www.maf.govt.nz/acvm/) or from:
Karen Crawford
ACVM Group
Post Office Box 2526
Wellington, New Zealand
Phone: 04 460 8750
Fax: 04 460 8771
Email: gandhia@maf.govt.nz
Final versions of the above mentioned documents will be made available on the website by early July. Copies of these may be downloaded at no cost. Hard copies will be made available at a cost of $7-$23 (plus GST) depending on the size of the document. An order form will be included with the ACVM - Registration Information Requirements when it is posted.
The ACVM - Registration Standard for Toxicology will be made available along with the other documents. This standard has not been sent out for public consultation because the requirements contained in it are taken directly from the existing licensing and registration packages.
Clients are reminded that they should check with the ACVM Group or the website that they hold the current version of these documents before using them.
Because of the number of submissions received on the efficacy
standards, which were made available on 1 April 1999, the submissions report has been
delayed beyond the date notified in the previous issue of AgVetLink. This
information will be forwarded as soon as it becomes available.
Executive Summary :
Standards Submissions
INFORMATION REQUIREMENTS
MAF received twelve written submissions in addition to a number of verbal comments made during the presentation of these documents in Auckland, Wellington and Christchurch.
The comments indicated a number of key policy concerns, viz
The opportunity for provision of electronic data packages.
What international data packages would be acceptable.
Further clarification of the proposed application types and more clearly differentiating between a new application (Type A) and a major formulation change (Type C1).
How it was planned to deal with products that had been cross-referenced to a product that was no longer licensed.
Whether MAF should be using risk rather than only allowing data 10-15 years old to be used for cross-referencing.
When bioequivalence was to be used for cross- referencing.
The option of using a declaration like the NRA in Australia for minor formulation changes rather than percentage changes in non-active ingredients.
For provisional registrations (Type D) what level of chemistry and manufacturing data can be provided.
How the biosecurity risk was to be managed during the transition phase and when the applicant will need to apply to Biosecurity for approval once the Act is implemented.
Other comments were on operational uses of the information and editorial, data and documentation changes.
CHEMISTRY STANDARD
A total of 20 submissions were received from industry, 15 pertaining to policy issues and five editorial. The main issues identified were as follows:
Stability studies for veterinary medicines
Greater clarification was requested regarding standards for levels of impurities and photostability. The current relevant VICH Guidelines will be the standard adopted with respect to these issues.
Stability studies re plant compounds
Currently pesticide registration is based on accelerated studies, whereas the Standard requires both accelerated and real time studies to be provided. Data generated from accelerated studies will allow an interim shelf life to be set for both veterinary medicines and plant compounds.
Expiry dates for plant compounds
Industry identified the associated issues of safe and appropriate disposal of expired product. MAF is concerned that plant compounds meet their expiry specifications because the presence of storage related impurities impacts on the residue risk managed under the ACVM Act. Manufacturers therefore must show the product is within specification for the claimed shelf life; consequently, an expiry date is shown on product labelling.
Batch analyses
ARPPA proposed a mechanism by which application types require differing levels of batch and stability testing. This is still under consideration.
Information requirements for experimental use permits for plant compounds
Industry pointed out that a complete chemistry dossier is not always available or in existence at this level of product development. MAF will address this issue.
Biological products
Greater detail was requested for this class of products in both the standard and guideline.
The submissions were of a positive and constructive nature and many are being incorporated into the final standard.
TARGET ANIMAL SAFETY STANDARD
Fifty comments were received on policy and requirements issues. Fourteen other comments were made on editorial matters. The policy and requirements comments focused on the following aspects of the standard: (number of comments)
The need for Standard One to cover risks to animal welfare arising from the use of live animals for teaching, testing, research or trialling of veterinary medicines (11)
Standard One will be removed from the Target Animal Safety Standard and will be covered by Animal Ethics Committee approval, which should address MAF requirements. AEC approval will be required via ACVM - Registration Standard for Good Research Practices. The requirement that overseas studies must meet the New Zealand standard for animal welfare will be removed because it is not the ACVM Act's role to manage animal welfare in other countries.
The requirement to treat animals with 1x, 3x and 5x the maximum recommended dose rate when a new active ingredient is being studied (3)
This requirement will be expanded as follows:
"A safety study using multiples of the recommended doses (up to 5 times) for at least the proposed duration of use and the proposed administration rate is generally sufficient. In most cases, the combination of 1x, 3x and 5x the recommended dose is appropriate. However, when it is expected that 5x dosing would result in adverse effects, the following combination (1x, 2x, and 3x) would be accepted. Alternatively, when it is unlikely that adverse effects may result from the 5x dose, the applicant may choose to increase the dosing."
These are consistent with the Australian NRA requirements.
The requirement for 12 animals to be used in these studies (4)
This requirement has been revised to ten treated animals and five untreated controls. Comments were made that we should follow overseas regulatory authority guidelines on this matter.
Other comments related to the content of postmortem and clinical examinations, terminology and formulations being tested. These issues will be addressed where appropriate in the final review of the standard.
MANUFACTURING STANDARD
Twenty-five comments were received on policy and requirements issues. Seven other comments were made on editorial matters.
The policy and requirements comments focused on the following aspects of the standard: (number of comments)
Clear interpretation of levels of auditing intended to be applied to manufacturers is required (4)
Audits will be for assessment of compliance with the GMP standard. The size and complexity of an organisation, the manufacturing processes employed, the types of products manufactured, and the degree to which the guidelines have been adopted by the organisation will determine the time and expertise required for an audit. This is what has been referred to as the 'level of auditing'.
The frequency of audit is not clear (2)
The frequency will vary depending on the level of auditing. In some cases this will be yearly; for others it may be biennially. Audits of specific manufacturers will be conducted more frequently if a history of non-compliance develops.
It is not clear how MAF will approve overseas manufacturers or their imported manufactured products (6)
Overseas manufacturers will continue to be approved on the current basis, either through mutual recognition agreements for GMP assessment or by assessment of the site master file and information requested in the form Application for Approval to Manufacture Animal Remedies. This document is being amended for relevance to the ACVM Act. Overseas manufacturers need to show certificated compliance with the national equivalent standard (e.g. USA Code of Federal Regulations) for GMP adopted by the regulatory authority of the country of manufacture.
Should MAF concentrate on auditing (or testing) final batches rather than monitoring manufacturing systems to assure product compliance (2)
Regulatory authorities in the US, EU, Japan, Australia, New Zealand and other states have moved away from relying on batch testing either by themselves, or independent consultant testing organisations to provide assurance of product compliance. The main reasons were the costs, the time involved, the need to generate and maintain national standards and procedures, and disputes over the equilibration problems between different testing organisations. The emphasis has for a number of years been on the total quality approach of GMP, which includes regular appraisal of manufacturing and testing standards, procedures and activities to provide assurance that a manufacturer is operating competently to deliver compliant products.
A clear and consistently used definition of a manufacturer is required (4)
This comment is acknowledged. Some inconsistencies have emerged between documents. These will be corrected when the final glossary is developed. The definition of manufacturer will include all operations of purchase of materials , production/formulation, quality control, release, storage, and distribution of products and the related controls.
Other comments related to parallel importing, information waivers, similarity with the ERMA requirements, and difficulties of different terminology between agricultural chemical and animal health industries.
It is important to acknowledge the difference between parallel importing and parallel manufacture. Unapproved parallel manufacture is not provided for in the processes being developed under the ACVM Act.
All these issues will be addressed where appropriate in the final review of the standard. No comments were received on the guidelines document.
EFFICACY STANDARD FOR COCCIDIOSTATS
Thirty-five comments were received on policy and requirements issues. Another three comments were made on editorial matters.
The policy and requirements comments focused on the following aspects of the standard: (number of comments)
Statistical requirements (3)
The p<0.05 level seems to have been accepted. A suggestion has been made that more stringent significance be allowed to be used and that the particular p level should be quoted. These are acceptable but 0.05 will be retained as a minimum.
The need to prove that all active ingredients produce their expected effects in the case of fixed combination products (1)
The requirement has been removed as our emphasis is on the efficacy of the trade name product _ not necessarily of its components.
Other comments related to technical requirements. These issues will be addressed where appropriate in the final review of the standard.
GOOD RESEARCH PRACTICES STANDARD
Twenty-seven comments were received on policy and requirements issues. Five other comments were made on editorial matters.
The policy and requirements comments focused on the following aspects of the standard: (number of comments)
The need for introduction of a new GxP standard (9)
Comments ranged from relief that at last some guidance was being given to the feeling that we should adopt GLP and GCP, with a range of options between. This standard is not designed to replace GLP or GCP but to draw our minimum requirements from them. They are, in effect, the guidelines to this standard. Those trials conducted under GLP and GCP will satisfy the standard. This will be clarified in the revised standard which also will be renamed to avoid the GxP confusion.
Requirements for protocols will be removed as we are not approving them. However, reporting requirements will reflect what was previously asked for under protocols.
Other comments related to specific requirements of protocol and reporting. These issues will be addressed where appropriate in the final review of the standard.
BIOEQUIVALENCE STANDARD
Eleven comments were received on policy and requirements issues.
The policy and requirements comments focused on the following aspects of the standard: (number of comments)
The appropriateness of bioequivalence for all types of products (1)
We are currently consulting with the human medicine requirements to draw up a list of appropriate products for applying bioequivalence.
The necessity for bioequivalence to be shown in each target animal (2)
We are currently investigating the VMD discussions which were alluded to in the submission, and consulting with various experts on the implications of allowing a biological model.
Other comments related to the choice of reference product and to the addition of chemical equivalence requirements. These issues will be addressed where appropriate in the final review of the standard.
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