Published: 7 September 2017

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The Medsafe Files — Episode Four: New Medicines Assessment (Part 2)

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Prescriber Update 38(3): 43-44
September 2017

Quality ensures that a medicine does what it is supposed to do every time

The quality of a new medicine is assessed to ensure that it is safe and consistently effective to minimise adverse events. The quality section of a New Medicine Application (NMA) is split into two main parts. One part focusses on the active ingredient of the medicine and the other part on the final dosage form, including any excipients and fillers.

Medsafe evaluates both parts against national legislation and international guidance to ensure that:

• the proposed formulation of the medicine has been suitably optimised and is appropriate for the intended route of administration
• the manufacturing processes are suitable and limit any impurities
• sufficient testing is done during and after manufacture
• the analytical methods used for testing are valid
• there is consistency between different batches
• the physical, chemical and biological properties of the medicine meet the requirements for the specific dosage forms
• the proposed packaging is appropriate
• the shelf-life is well established.

The information required for a NMA is specific to the type of medicine (chemical, biological), dosage form (tablet, solution for injection) and classification (prescription, over-the-counter).

It also depends on the risk profile of the medicine. For example, the quality review of a prescription medicine that contains a new active ingredient (considered higher risk) relies extensively on comparison of the provided data against international guidance. However, in the case of a generic prescription medicine (considered intermediate risk), evaluations are largely based on existing knowledge and comparisons with the innovator medicine that was originally approved. This has implications for the degree of clinical data required, as discussed in the next section.

The safety of new and generic medicines is established in different ways

For a new medicine (one that has not previously been approved in New Zealand), the results of full clinical trials are evaluated (see the previous edition of Prescriber Update)¹. These trials have been carried out in human patients. The sample size, demographics and disease states are selected depending on the medicine’s phase of development and intended use.

The main purpose of these clinical trials is to completely characterise the medicine’s safety, efficacy and pharmacokinetic profile. However, for a new generic medicine, a specific type of clinical trial is used instead: bioequivalence studies.

Bioequivalence studies are based on the concept that if the systemic concentration of a generic medicine, once administered, is the same as the innovator then it will have the same therapeutic effect. This conclusion is made on the condition that the two medicines are the same in every other way, underlining the importance of quality assurance.

Bioequivalence studies are carried out with healthy human subjects and involve determining the amount of active ingredient present in the blood over time. Some dosage forms generally do not need these studies to establish bioequivalence (eg, injections), while others require multiple trials under different conditions (eg, modified release tablets). Further information on generic medicines and bioequivalence can be found in a previous edition of Prescriber Update (www.medsafe.govt.nz/profs/PUArticles/Mar2013GenericMedBioqueivalence.htm).

All clinical studies (including bioequivalence studies) must receive ethics approval and adhere to Good Clinical Practice, as discussed previously in The Medsafe Files — Episode Two².

Ensuring the safety of a medicine is not limited to the product itself

Beyond pharmaceutical chemistry and clinical performance, several other aspects of a new medicine are regulated to enhance patient safety.

To minimise the likelihood of medication errors, Medsafe undertakes a thorough review of the proposed name of the medicine, how it is labelled and the supporting documentation produced by the company to ensure its correct use (data sheet and consumer medicine information).

The site(s) where the medicine is manufactured, tested and packaged are also inspected to ensure that they comply with the requirements of Good Manufacturing Practice (GMP). GMP will be described in more detail in the next edition of Prescriber Update.

The outcome of Medsafe’s evaluation — approval or referral

Following the assessment of an NMA, Medsafe provides advice to the Minister’s delegate on whether the medicine has an acceptable risk/benefit profile. If it does, consent will be granted for distribution of the medicine in New Zealand.

If the safety, efficacy and/or quality of the medicine is not considered to meet the required standards, the NMA is referred to the Medicines Assessment Advisory Committee for further review (refer to The Medsafe Files – Episode Four, Part 1 for more information)¹.

References

1. Medsafe. 2017. The Medsafe Files — Episode Four: New Medicines Assessment (Part 1). Prescriber Update 38(2): 27–8. URL: www.medsafe.govt.nz/profs/PUArticles/June2017/TheMedsafeFiles.htm (accessed 4 August 2017).
2. Medsafe. 2016. The Medsafe Files — Episode Two: Clinical Trials. Prescriber Update 37(4): 54. URL: www.medsafe.govt.nz/profs/PUArticles/December%202016/ClinicalTrials.htm (accessed 4 August 2017).