52. FOI 3471 shows contamination in the batches. Why didn’t the TGA undertake whole genome sequencing on the batches when it was an obvious way to look for contamination? 53. As per the TGA FOI disclosure log that some batches had up to 40% degraded mRNA – what are the potential risks of degraded mRNA in the body and what studies were carried to determine the safety of degraded mRNA? 54. How does the TGA know degraded mRNA isn’t going to produce toxic proteins? 55. How did the TGA undertake batch testing. Are all vials tested and what were the benchmarks especially in regards to tolerance levels? 56. Did the Covid-19 vaccine trail undertaken by Pfizer use batches made via the commercial process or the laboratory process? Are there trials undertaken by Pfizer using the commercial process and if so can they be provided? 57. Can the TGA report batch numbers by number of reported adverse events and reported deaths so people can see which batches had the highest rate of adverse events? 58. Could the TGA please provide evidence that the Covid vaccine batches had the same purity in Australia as what was stated in the manufacturing facility. Could documentation of the signatures and percentage of intact mRNA by both the manufacturer and the TGA please be provided? 59. Why did the TGA approve batches with as low as 60% integrity and how can it guarantee safety of those batches from degraded mRNA and further degradation after transport? 60. Why is the integrity level of batches commercial in confidence? This is a safety issue that Australians should be aware of it is it not? 61. If a batch is only 60% intact and each vial contains 5 doses how can the TGA be sure that every person is getting a consistent dose? 62. FOI 2389-3 page 110 Table 2 says concentration depends on batch size? How can the TGA be sure that every person is getting a consistent dose?

Question Number: 170
PDR Number: SQ22-000539
Date Submitted: 21/11/2022
Department or Body: Department of Health

52. The testing results for the specific batches referred to in FOI 3471 met all required specifications and did not suggest any contamination.

53. Animal toxicity studies with vaccine batches with a similar degradation profile to the commercial batches raised no safety concerns. The findings were related to immune responses (e.g. inflammation the injection site, hypercellularity of lymphoid tissues), plus minimal transient, reversible vacuolation in the liver. Batch release studies involve in vitro translation studies for the mRNA in each batch. No truncated or toxic proteins were found.

54. See response to Question 53.

55. The Therapeutic Goods Administration (TGA) does not open and test all vials in a batch as this is logistically impossible given it would involve opening and testing millions of vials and would compromise their sterility and delay availability to patients. TGA batch release for COVID-19 vaccines involves performing multiple tests across multiple vials of vaccine which are drawn from the manufactured batch. When establishing the required specifications i.e. tolerance intervals, a range of data submitted by the Sponsor is reviewed. This includes process and testing data gathered through development and refinement of the manufacturing process (including stability during transport and storage), and various laboratory and clinical studies consistent with international guidelines. Collectively, this means that batches which meet the approved and evidence-based specifications will be of acceptable quality, safe and effective.

56. As is usual during the development of a vaccine, Pfizer submitted documentation to describe the development history of the finished vaccine product. The formulations and processes have remained the same throughout the vaccine development, except for necessary changes to the scale as development has progressed from initial clinical supplies for the clinical trials (small batches) to commercial manufacture (large batches). Batches of vaccine used in clinical studies were directly comparable to large scale commercial batches. Batches used in clinical studies were not manufactured using a laboratory scale process. Information regarding the outcomes of clinical trials conducted are available in the Product Information for the respective products published on the ARTG, available at: www.tga.gov.au/resources/artg.

57. Information relating batch numbers to adverse events has been released under FOI (see FOI 3545 in the TGA disclosure log at: www.tga.gov.au/foi-disclosure-log). However, assessing batch safety on the basis of the number of fatal adverse event reports associated with a batch is not a reliable indicator of safety. The nature of the adverse event reports would need to be considered, as well as other factors that may confound the interpretation of the data. For example, the size and/or distribution of the batch may influence reporting numbers as different batches may have been used in different populations, such as aged care facilities earlier in the roll-out. To date, the TGA has not identified a safety signal indicative of a quality issue for any particular batch of a COVID-19 vaccine.

58. The TGA batch release process reviews the manufacturers testing results, comparable overseas regulatory laboratory testing results (when available) and TGA Laboratories own testing results. TGA reviewed purity test result data from the manufacturer and the TGA Laboratories for abnormal trends and to ensure results are similar from both sources. To date all batches of COVID-19 vaccines have met the required purity specifications and there have been no anomalies in the comparative and trend analysis. The requested documents for individual test results are considered commercial in confidence material and therefore cannot be released unless agreed by the Sponsor.

59. The TGA reviews a range of data submitted by the Sponsor before approving specifications for mRNA vaccines. This includes process and testing data gathered through development and refinement of the manufacturing process (including stability during transport and storage), and various laboratory and clinical studies in keeping with international guidelines. Collectively, this means that batches which meet the approved and evidence-based specifications will be of acceptable quality, safe and effective. This approach was taken when establishing an acceptable specification for the purity and integrity of the mRNA COVID-19 vaccines.

60. The manufacturing process and individual testing methods developed by the manufacturer are commercially sensitive material. While specification limits are are manufacturer-specific, the TGA reviews the compliance of every batch seeking to be supplied in Australia with the approved specification limits. In addition, the TGA compares the manufacturer’s testing results with those obtained from the TGA Laboratories independent testing. To date over 166 batches of mRNA COVID-19 vaccines have been assessed by the TGA with all batches meeting the approved specification for RNA integrity.

61. Specific instructions are provided in the Product Information for the end user to ensure that the product in each vial is diluted and mixed correctly. The approved and evidencebased specifications ensure each vial will be of acceptable quality, safe and effective. All batches of mRNA COVID-19 vaccines have met the specification for purity and integrity.

62. The statement “Depending on batch size” refers to early development batches compared to later development or commercial scale batches which differed in their respective concentrations. Therefore, the concentration of the drug substance does not change or depend on the batch size with respect to what is manufactured and released. To ensure vaccine and dose consistency, the TGA independently assesses the quality of every batch of COVID-19 vaccine supplied in Australia to ensure that the concentration is within approved specifications. For the end user, specific instructions are provided in the Product Information to ensure that the product is diluted, mixed and administered correctly so that each dose contains similar amounts of mRNA (Refer to responses for Questions 178 and 181).