It’s here! PSA has released its Australian Pharmaceutical Formulary 25th Edition (APF25). I was really intrigued to see what the “expanded section on compounding” was going to look like. It is a very welcome update introducing a much more detailed section on complex compounding, clarifying some old misconceptions. So, what do you need to know?
Pharmacists legal obligations for complex compounding remain the same. Compounding pharmacists still operate under an exemption from the TGA however, the APF25 has broken down what parts of the Therapeutic Goods Act pharmacists are actually exempt from. The Therapeutic Goods Regulations specifies that pharmacists are exempt from requiring a Licence to Manufacture and entering products they produce onto the ARTG. These exemptions cover pharmacists and medicines when they;
Are not biologicals as defined by the Therapeutic Goods Act
Prepared by pharmacists in a pharmacy open to the public or on the premises of a private hospital, and supplied on or from those premises, and not supplied on a wholesale basis, or employed by a public hospital or public institution, for supply in hospitals or public institutions in the same state or territory
Prepared for a specific patient in response to an identified need.
But what a lot of pharmacists may have missed in the past is that pharmacists are NOT exempt from the quality standards and advertising requirements of the Therapeutic Goods Act. The APF25 has now included a section regarding quality standards stating that
“Compounded medicines must meet the quality standards set out in Section 10 of the Therapeutic Goods Act...”.
Section 10 of the Therapeutic Goods Act 1989 is found in chapter 3, part 3-1. It details the expectations of quality for all medicines in Australia. The TGA does not require pharmacists to test every product they make, however, they expect that if the product was tested it would meet the relevant label claims and pharmacopeial standards, for example, the concentration of an active pharmaceutical ingredient (API).
Another interesting addition to the legal obligations is the addition of a statement regarding repackaging APIs. It is not unusual for larger compounders to purchase large containers of API to keep the cost down, but may dispense the products into smaller containers for ease of use or to be used in different lab areas. Pharmacists are reminded that repackaging is a step-in manufacturing and requires a manufacturing license. In fact, repackaging is the step of manufacturing that the major Australian suppliers in compounding are licensed for! Stability information for API supplied by manufacturers is based on the containers supplied which can arguably change when packaging changes. There are many considerations for storage and stability which can actually extend to personnel safety issues and not just stability and quality of the API.
There is also the addition of biologicals (according to TGA) and gene therapies which are not to be compounded without appropriate manufacturing licenses or accreditations.
A new change to the section which is an interesting one and probably of the biggest conversations in compounding. Expiry dates. The new APF25 states that the expiry date is 28 days or less from the date the medicine is compounded unless otherwise specified in the APF or a reliable stability study. In previous versions, the pharmacist was able to make an informed decision on expiry dates using “reliable literature”. This included United States Pharmacopeia and peer-reviewed journals which the pharmacist could then use to come to a decision using the nature of the drug and dosage form, the potential for microbial growth, final containers used, storage conditions and duration of treatment.
The pharmacist is now restricted to using a reliable stability study that uses the same formulation, packaging and storage conditions as the compounded medicine. If the expiry date differs from the expiry date guidance in the APF (longer or shorter), the expiry date from the stability study should be used.
For example; if you have a stability study indicating 70 days expiry for a 2mg/mL omeprazole suspension and a study indicating the same for 5mg/mL omeprazole suspension, by this logic the stability data does not apply to a 3mg/mL omeprazole suspension which would have to bear a 28-day expiry. While I can understand the sentiment, the wording is quite restrictive, and it can certainly be argued that it is more favourable to commercial interests than actual patient safety.
The previous version of the APF did not refer to a specific margin of error simply stating that weighing equipment must be appropriate for the weights being measured. This new version of the APF explicitly states that they recommend a 2% margin of error and that the minimum weighable quantity should be calculated accordingly. This is something that is discussed in practice quite often, but there hasn’t been explicit guidance on the use of MWQs. If you need help with your MWQ calculations, your balance supplier should be able to provide you with the balance sensitivity.
Quality Control & Testing
As mentioned, pharmacists are not expected by the TGA to test every product, but they do expect the products to pass if they were to be tested. APF24 mentions that the testing of ingredients and finished compounded goods should be done based on risk assessment. The new version states a requirement for external analytical testing.
“Samples of complex or high-risk compounded medicines that are commonly prepared should be submitted to an appropriately accredited analytical laboratory for testing according to documented testing protocols. Samples prepared by each compounding staff member should be tested to demonstrate reproducible practices between individuals.”
The appropriate accreditation of analytical laboratories is only touched on in the quality control section, however, the new Quality of Ingredients section does explicitly state that “the pharmacist should have the ingredient tested by a laboratory holding appropriate credentials for testing (e.g. accredited by the National Association of Testing Authorities (NATA) or licensed by the TGA)..” when concerned about the legitimacy of a certificate of analysis.
Using a lab that is NATA accredited or TGA licensed means that they have received external recognition for their competency in particular tasks. A NATA accreditation or TGA license are not sweeping statements about all services they conduct, some companies may opt to only accredit particular types of testing – for example, they could be licensed/accredited for chemical testing, but also conduct microbiological testing. If you want to assess a lab for appropriateness, one of these accreditations or licenses is an easy way – but be sure to check the details about what activities are covered. This is easily accessed on the TGA eBS. It is possible to do your own audit and validation of the service asking questions about their quality management systems, competencies and lab systems.
The frequency of testing requirements may depend on your state guidance or your QCPP accreditation status.
Compounding Sterile & hazardous medicines
The previous version of APF included details about sterile and hazardous compounding however this was littered throughout the different sections. The APF25 has allocated a specific section to cover the additional requirements of these higher-risk activities making it clearer to those who are using them. The list of medicines considered hazardous by the APF may seem short when looking at the 4 point list in this section, however, point 4 refers to a 300+ list of medicines. Be sure to check your practice for these products as it is often missed that hormones are in fact hazard products. The mention regarding appropriate standards helps to create a more uniform expectation across the professional guidances linking back to the PBA guidelines.
We are far from a perfect system in Australia with a number of standards, guidelines, references and commercial interests contradicting and cross-referencing each other. But these changes in the APF25 are very welcome and I believe are a truly earnest effort to create a comprehensive standard for our Australian pharmacists. If you would like help to apply these new requirements or decipher what they mean for your practice, let's book in a FREE 30 min Compounding Assessment!