Amendments foreshadowed to BP tests

The TGAL Microbiology Section has recently sought clarification from the British Pharmacopoeia Commission on the following points relating to methods described in the BP 1998 for the Test for Sterility and Test for Efficacy of Antimicrobial Preservation:

• Table 16A-3 of the BP 1998 Appendix XVI A Test for Sterility states the minimum number of items recommended to be tested for each medium from each batch. For parenteral preparations where the batch size is more than 500 containers, the BP 1998 specifies a sample size of 30 containers whereas the EP Third Edition Supplement 1998 specifies a sample size of 20 containers.
• Table 16C-1 of the BP 1998 Appendix XVI C Test for Efficacy of Antimicrobial Preservation specifies the acceptance criteria for parenteral and ophthalmic preparations. Criteria B specifies a 2 log reduction at 14 days with no increase at 28 days for fungi whereas the BP 1993 and EP 1998 both specify a 1 log reduction at 14 days with no increase in numbers at 28 days.
• Table 16C-3 of the BP 1998 Appendix C Test for Efficacy of Antimicrobial Preservation specifies the acceptance criteria for topical preparations which is consistent with that specified in the BP 1993 but not consistent with the acceptance criteria for topical preparations that were later specified in the BP 1993 Addendum 1995 and the EP 1998. Both the BP 1993 Addendum 1995 and the EP 1998 specify A and B criteria for topical preparations whereas Table 16C-3 of the BP 1998 specifies only one acceptance criteria for topical preparations.

The British Pharmacopoeia Commission Secretariat have confirmed that the acceptance criteria in Table 16A-3 of Appendix XVI A Test for Sterility and Tables 16C-1 and 16C-3 of Appendix XVI C Test for Efficacy of Antimicrobial Preservation should be those of the EP and that suitable amendments will be included in Amendments No. 1 to the BP 1998 to be published later this year with an effective date of December 1, 1998.

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European Pharmacopoeia adopts TGAL method as candidate for official reference

A method developed by the Blood Products Group in TGAL's Molecular Biology Section is the subject of a European Pharmacopoeia collaborative study to assess its suitability for inclusion in the Pharmacopoeia as the reference method. The method measures the potency of Anti-Rh (D) immunoglobulin, a plasma product given to rhesus negative women. The product is used to prevent immunisation during pregnancy that can lead to severe problems in babies of subsequent pregnancies. Australia uses 60,000 doses of this product yearly. The method currently used to assess potency is laborious and imprecise and the EP is anxious to adopt a satisfactory method.

Following preliminary results which were published in TGAL's Laboratory Information Bulletin last year, the method was the subject of an EP discussion paper during the EP's Group of Experts on Blood Products meeting in Strasbourg in April 1998. As a result, TGAL was appointed as one of two centres to collaborate on further development and coordinate an international exercise to test the method's viability. Satisfactory results are expected to lead to the method's formal adoption as the EP reference method over the next year.

FDA workshop on method validation and worldwide trends in evaluation of HPLC performance

The 22nd symposium on HPLC (High Performance Liquid Chromatography) held on May 2 - 8 1998 at St Louis, Missouri, USA included a one-day workshop on HPLC method validation run by the US FDA and a session on system suitability as a measure for checking HPLC performance.

The FDA's workshop covered subject matter similar to that included in courses offered by the Chemistry Section of TGAL but lacked TGAL's practical "hands on" classes. The course was designed for the local US industry with a particular emphasis on FDA and USP perspectives but included a thorough comparison of the ICH (International Conference on Harmonisation) and USP guidelines. In ICH guidelines the USP terms "Ruggedness" and "Robustness" have been combined as Robustness and a new parameter "System Suitability" has been added.

The use of system suitability has grown enormously in recent years to assess the performance of HPLC systems. This shift from process control to performance control has been made necessary by the proliferation of different brands of HPLC columns. Column performance is assessed during each analysis by determining the relative standard deviation of response factors and retention times, capacity factor (k'), efficiency (N), symmetry factor (f), and resolution factor (R) of the analyte peak. With access to various software packages, these parameters can easily be monitored throughout the run. The system suitability criteria should be designed and established during the method development and validation processes but changes in column packing during use may require some ongoing method adjustment. It will be necessary therefore to distinguish between method adjustment and modification. Some guidance on this topic is provided in an article by William Furman, John Dorsey and Lloyd Snyder in the June issue of Pharmaceutical Technology page 58.

Well designed system suitability tests are excellent tools to control system performance and are included in some recent compendia monographs. When they are included in all methods, the value of the method specified in the Appendix D to the Code of GMP may be limited to serving as a diagnostic tool to differentiate between column and system problems.

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Medical device incident report investigation scheme moves to TGAL

The Medical Device Incident Reporting Scheme has been moved to the Biomaterials and Engineering Section of TGA Laboratories. The move took place in response to a restructure of the Medical Devices Section, Conformity Assessment Branch, which now deals only with premarket evaluation of medical devices. The move will strengthen the link between this activity and other TGAL activities. The close links with Recalls, Surveillance, GMP and the Medical Devices Section will be maintained.

Dr Jorge Garcia has been appointed as manager for the scheme. Jorge has had many years of experience as a medical device problem report investigator and in the field of biomaterials research. In 1997, Jorge spent two months at ECRI learning about systems and techniques for device problem, accident and forensic investigations. Methods for problem investigation are currently under review.

New appointment in blood regulation

Dr Albert Farrugia has been appointed as Senior Advisor in Blood Products to head a new Blood Products group which is being established for an initial period of 2 years. Albert comes to this position from a strong background in Transfusion Medicine, which has included heading the Blood Products Unit within Molecular Biology over the past three years as well as long periods in many areas of the industry.

Over the next two years, the Blood Products Group will coordinate TGA's response to a number of new initiatives in the regulation of blood products, implementing the blood-related recommendations of TGA's Tissue Regulation Working group and several other TGA initiatives. These include steps to adapt international regulatory guidelines for use in Australia, liaison with the Health Services Development Division of the Department of Health and Family Services in the establishment of a national reserve of plasma products and a list of alternative plasma products for use in situation of chronic and acute shortage and liaison with the Australian Red Cross Blood Service recently established as a national body.

The new group will be jointly resourced by the Molecular Biology and Immunobiology Sections of TGAL and a contract from HSDD. Dr Brian Hillcoat has been appointed by DSEB as Senior Clinical Advisor in Blood Products to provide clinical advice to the Blood Products Group and Stream 4 of DSEB. Dr Nagendram Nandapalan from the Immunobiology Section has also joined the group. Dr Nandapalan is also TGAL's Principal Viral Safety advisor and has a strong background in immunology, areas which fit in naturally with the group's role.

PB listing cut-off dates

The process of listing a product with the Pharmaceutical Benefits Scheme includes the provision of a sample for analysis by the TGA Laboratories. To assist in meeting listing deadlines an agreement has been reached with sponsors whereby samples will be supplied no later than 1 month prior to the closing date for those samples where chemical testing is required and no later than 6 weeks prior to the cut-off date for samples involving microbiological testing.

The following table sets out the dates by which samples should be provided to the laboratories for analysis prior to listing as pharmaceutical benefits.

Publication Date	Chemistry Deadline	Microbiology Deadline
February 1999	22 October 98	8 October 98
May 1999	22 January 99	8 January 99
August 1999	22 April 99	8 April 99
November 1999	22 July 99	8 July 99
February 2000	22 October 99	8 October 99
May 2000	22 January 2000	8 January 2000