ADEC meeting dates

Australian Drug Evaluation Committee (ADEC) meeting dates for 2000

MEETING NUMBER	CUT-OFF DATE	MEETING DATE
2000/1 (208)	11 January 2000	10-11 February 2000
2000/2 (209)	14 March 2000	6-7 April 2000
2000/3 (210)	16 May 2000	8-9 June 2000
2000/4 (211)	11 July 2000	3-4 August 2000
2000/5 (212)	12 September 2000	5-6 October 2000
2000/6 (213)	14 November 2000	7-8 December 2000

Pharmaceutical Subcommittee (PSC) meeting dates for 2000

MEETING NUMBER	CUT-OFF DATE	MEETING DATE
2000/1 (70)	13 January 2000	31 January 2000
2000/2 (71)	9 March 2000	27 March 2000
2000/3 (72)	11 May 2000	29 May 2000
2000/4 (73)	6 July 2000	24 July 2000
2000/5 (74)	7 September 2000	25 September 2000
2000/6 (75)	9 November 2000	27 November 2000

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Drug master file and certificate of suitability of monographs of the European Pharmacopoeia

Sponsors are aware that where an organic active raw material used in product manufacture is sourced from a third party manufacturer, the data is submitted via a European-formatted Drug Master File (DMF). However, for an active raw material that is the subject of a monograph in the European Pharmacopoeia (EP), the EC guideline entitled "Requirements In Relation To Active Substances" (part 4.5.1) allows the submission of a Certificate of Suitability of Monographs of the European Pharmacopoeia (CoS) in lieu of a DMF. Except for antibiotics, DSEB accepts the CoS in lieu of a DMF for organic active raw materials, including amino acids. For antibiotics, a CoS will be accepted but must be accompanied by a DMF.

Where a CoS is provided in place of a DMF, the following must also be submitted concurrently:

• An outline of the route of synthesis.
• Evidence of GMP for the sites of manufacture.
• An assurance that any conditions/additional tests attached to the CoS by the issuing authority are applied to each batch.
• An assurance that agreed tests additional to those in the CoS (eg particle size test and limits, specific polymorphic form) are also conducted.
• Part A of the evaluation report on the active raw material. [The manufacturer of the active raw material can obtain Report A from the European Department for the Quality of Medicines (EDQM, the issuer of the CoS).]

In addition, for an application to be effective, TGA needs the information and assurances sought in Forms 6A and 6B of Appendix 6 of the AGRD Volume 1, the Manufacturer's Form and the Sponsor's Form respectively. For drugs evaluated by the Drug Safety and Evaluation Branch, Volume 1 of the AGRD sets out the form in which information is to be submitted so that the application meets the requirements of Subsection 23(2) of the Therapeutic Goods Act 1989.

Editorial changes to Product Information

Changes to Product Information texts (PIs) that do not require evaluation are known 'in house' as TYPE 8G APPLICATIONS.

An 8G Application does not attract an evaluation fee, but does attract a nominal processing fee (equivalent to the Safety Related Notification fee), currently set at $500 per application. The application is recorded by the TGA but it is not given an Application Number.

The only changes that are acceptable as a Type 8G Application are minor editorial changes such as grammatical corrections, the deletion of redundant text or format changes (made in line with Section 4.20 of the Australian Guidelines For The Registration of Drugs - Volume 1 - Second Edition, July 1994). For example, the deletion of a pack size that is no longer marketed or registered is acceptable as an 8G Application. The addition of a CAS No. or a chemical structure is not acceptable under this procedure.

The editorial changes that are not acceptable as an 8G Application (because they require evaluation) involve any changes relating to the chemical, biological or clinical content of the PI. That is, any scientific change to the PI is not acceptable as a Type 8G Application. Cloning statements from another approved PI and the merging of two separate Product Information texts into one are also unacceptable.

The TGA has encountered problems in the past where 8G Applications for "editorial" changes to the PI have required evaluation. Part 2 changes may have clinical repercussions. For example, the deletion of a multi-dose pack may not justify the "editorial" removal of clinical comments or warnings regarding multi-dose use and would require more than just "editorial" consideration.

Safety Related Notifications are best submitted separately from other kinds of applications, especially Type 8G, as discussion of the 8G may confuse the applicant about the status of the Safety Related Change. Do not use Type 8G Applications to augment other PI changes such as Pharmaceutical changes or Safety Related Notifications.

In accordance with Section 28(3) of the Therapeutic Goods Act 1989, the TGA makes an appealable decision on an 8G Application and notifies the Sponsor in writing. However, in the case where the decision is positive, the date of the last TGA approval annotated on the Product Information document does not change because an evaluation has not been conducted.

A separate article on Safety Related Notifications <http://www.tga.gov.au/docs/html/tganews/news36/med.htm> will appear in a later edition of TGA News.

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European Union (EU) guidelines

Following consultation between the Drug Safety and Evaluation Branch (DSEB), the TGA Laboratories Branch (TGAL) and the Australian Pharmaceutical Manufacturers Association (APMA), the TGA has decided that the following European Guideline should be adopted in Australia. The EU Guidelines are generated by the Committee for Proprietary Medicinal Products/International Conference on Harmonisation (CPMP/ICH) and are to be regarded as part of Volume 1 of the Australian Guidelines for the Registration of Drugs (AGRD). The guideline included in this edition of the TGA News will also be included in the next edition of Volume 1 of the AGRD.

The Guideline will be adopted with effect from 1 January 2000.

Ref. No. CPMP/ICH/366/96
Addendum to Note for Guidance on Dose Selection for Carcinogenicity Studies of Pharmaceuticals: Addition of a Limit Dose and related Notes

Self-assessable change notification (SAN)

Guidelines in Appendix 8 of the AGRD Vol 1 July 1994 edition allow sponsors of registered products to make certain changes to the chemical and pharmaceutical (part II) data without prior approval from the TGA. This is the so-called self-assessable change procedure, which has its legal basis in Sections 28 and 32 of the Therapeutic Goods Act 1989. Sponsors must comply with certain general and specific conditions and, in most cases, notification to the TGA is required. Since its introduction, self-assessable change notification (SAN) has operated successfully and has been well received by industry. It has allowed sponsors to make timely changes to their registered products without waiting for prior approval from the TGA and this in turn has reduced the evaluation work load at the TGA.

Because self-assessment of validation data is involved, the integrity and success of this method of making part II changes can only be guaranteed by very strict adherence by sponsors to the conditions laid down in the Appendix 8 guidelines. Failure to comply with the guidelines may compromise the quality and safety of a drug product.

To ensure continuation of the self-assessment system, sponsors are reminded of the following:

• Notification of a self-assessable change should be either prospective or as soon as possible after implementation, and certainly within two months of implementation. Any delay in notification beyond two months of implementation is a breach of the general conditions of these guidelines.
• All of the specific conditions particular to the change(s) should have been met before they are implemented. In this regard, any validation data required must have been generated prior to the notification, and must be in the possession of the Australian sponsor making the self-assessment. An assurance that such data will be generated or that such data have been generated and reviewed by an overseas affiliate is NOT acceptable. The local sponsor must accept full responsibility for review of the validation data.
• Where comparative data is required to validate a change, sponsors should check carefully that the data have been generated in accordance with Note N.1 and Note N.5 of the Appendix 8 guidelines. The validation data represent the minimum specified and any additional necessary validation data such as those required by the code of GMP must also be conducted.
• Sponsors are not to "vary" any set of specific conditions on their own volition simply because they deem a particular change to be "truly minor". Where, for whatever reasons, a sponsor does not wish to generate the necessary validation data specified in a self-assessable change, the option is available of presenting "amended" validation data as spelled out in Section 1.4 of Appendix 8. Note however, that this will render the proposed change(s) not self-assessable and requiring prior approval from the TGA. A Category 3 or a Category 1 application (as applicable) will be required.

Sponsors who are unsure of the procedures or are uncertain as to which specific conditions apply in a particular case should approach the TGA for advice in the first instance rather than risk breaching the conditions laid down in the guidelines (Appendix 8), and to be consistent with the Therapeutic Goods Act 1989.