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OTC medicines - Safety and efficacy data

30 November 2015

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2 - OTC generic medicines

In most cases you do not need to provide safety or efficacy data in support of OTC generic medicines. However, in some cases you may need to provide bioequivalence data or therapeutic equivalence data to demonstrate bioequivalence or therapeutic equivalence with the originator medicine.

To determine if you need to provide bioequivalence or therapeutic equivalence data:

In rare cases where supporting data for the originator medicine are 'protected', we require full efficacy and safety data. This applies where the active ingredient was first included in an Australian medicine within the last five years (Section 25A of the Therapeutic Goods Act 1989 refers).

2.1 Generic oral medicines

When bioequivalence data (or justification) are not required

You do not need to provide bioequivalence data, or a justification for not providing this data, if any of the following apply:

  • The medicine is an oral medicine and there are other corresponding OTC generic medicines registered on the ARTG that have been approved without either:
    • bioequivalence data (not including N1 application approvals)
    • a justification for not providing bioequivalence data.
    The large number of OTC medicines that fall into this category are detailed under Generic oral medicines that do not require bioequivalence data.
  • The medicine is an aqueous oral solution at the time of administration and both:
    • the active substance is in the same concentration as a currently registered oral solution
    • the excipients do not significantly affect: gastric passage or absorption of the active substance or in vivo solubility or in vivo stability of the active substance (provide justification or evidence to support this).
  • The medicine is an oral medicine containing active ingredients that are not absorbed (e.g. barium sulphate, simethicone and alginic acid).
  • The medicine is for oral topical use and is intended to act without systemic absorption. However, you may need to provide therapeutic equivalence data - see Generic topical (locally acting, locally applied) medicines.
  • The medicine differs from a fully evaluated and registered medicine only by way of a minor difference in formulation of the colouring agents, printing inks, flavours or fragrances, that are present at not more than 2% w/w/ or w/v (e.g. a new flavour being added to an existing range).
  • The medicine has an acceptable correlation between the rate and extent of in vivo absorption and the in vitro dissolution rate, and the in vitro dissolution rate of the new medicine is equivalent (under the same test conditions used to establish the correlation) to a registered medicine.
Generic oral medicines that do not require bioequivalence data

Unless the exceptions below apply, you do not need to provide bioequivalence data (or a justification for not providing this data) for generic immediate release or enteric coated oral dose form medicines (e.g. tablet, capsule, oral liquid or suspension) that only contain one or more of the following active ingredients:

  • Aspirin
  • Bisacodyl
  • Bromhexine hydrochloride
  • Brompheniramine maleate
  • Caffeine
  • Chlorpheniramine maleate
  • Codeine phosphate
  • Dexchlorpheniramine maleate
  • Dextromethorphan hydrobromide
  • Dimenhydrinate
  • Diphenhydramine hydrochloride
  • Docusate sodium
  • Doxylamine succinate
  • Guaiphenesin
  • Hyoscine butylbromide
  • Hyoscine hydrobromide
  • Ibuprofen
  • Ibuprofen lysine
  • Ibuprofen sodium
  • Loperamide hydrochloride
  • Mebendazole
  • Naproxen
  • Naproxen sodium
  • Paracetamol
  • Phenylephrine hydrochloride
  • Promethazine hydrochloride
  • Pseudoephedrine hydrochloride
  • Ranitidine hydrochloride
  • Sennosides
  • Triprolidine hydrochloride
Exceptions

Even if the ingredient is listed above, you will still need to provide bioequivalence or other clinical data (or a justification for not providing such data) when:

  • Your application includes a request for a brand equivalence statement for the purposes of Pharmaceutical Benefits Scheme (PBS) listing.
  • there is reason to consider that bioavailability of the medicine differs from existing medicines so as to adversely impact on efficacy and/or safety (e.g. it contains excipient(s) or has novel properties that could significantly affect gastric passage, absorption, in vivo solubility or in vivo stability of the active substance). Contact OTC Medicines if you are unsure.

Note: If a new originator combination medicine containing active ingredients from the above list was approved, bioequivalence data (or justification for not providing) would be necessary in support of subsequent generic applications.

When bioequivalence data (or justification) are required

Provide bioequivalence data (or a justification for not providing) if your medicine does not meet the criteria described in When bioequivalence data (or justification) are not required. Contact OTC Medicines if you are unsure.

Requirements for bioequivalence studies

Study requirements are described in:

Include biopharmaceutic study reports in CTD Module 5.3.1.

Complete the Summary of a Bioavailability or Bioequivalence Study form for each study and include in CTD Module 1.11.1.

Choice of reference medicine

You will need to demonstrate bioequivalence against the corresponding strength of the originator medicine as marketed in Australia. If you are unsure of the identity of the originator medicine, contact OTC Medicines.

We will accept bioequivalence studies carried out using samples of the originator medicine obtained from outside Australia if you, as the applicant, can provide robust scientific evidence that the overseas and Australian reference products are identical. See Biopharmaceutic studies for details of the evidence required.

Justifications for not providing bioequivalence data

Include a justification if you are not providing bioequivalence data when it would normally be required.

Ensure your justification addresses all issues as outlined in both:

Include the justification and copies of any cited literature in CTD Module 1.9.2.

If we do not accept your justification and you subsequently wish to provide bioequivalence or other clinical data, this will need to be provided as part of a new application.

Related information and guidance

For generic OTC medicines that require bioequivalence data:

2.2 Generic topical (locally acting, locally applied) medicines

The safety and efficacy of topical medicines may be influenced by the excipient formulation. For example, different excipients may significantly affect the release of active substances from the formulation or the penetration of active substances into the skin.

For many OTC topical medicines that have a long history of use, often in a range of different formulations, safety and efficacy can be sufficiently assured and provision of supporting data are not required.

For some generic topical medicines, you will need to demonstrate therapeutic equivalence of the proposed medicine to the originator medicine.

When therapeutic equivalence data are not required

You do not need to provide safety or efficacy (therapeutic equivalence) data for the following topically-applied ingredients or medicine categories, provided the medicine is a true generic (i.e. same strength, pharmaceutical form, directions, indications) and it is conventionally formulated:

  • Antibacterial and/or anaesthetic and/or anti-inflammatory throat lozenges (containing amylmetacresol, dichlorobenzyl alcohol, cetylpyridinium chloride, benzydamine hydrochloride, benzocaine, hexylresorcinol, benzyl alcohol, lignocaine hydrochloride)
  • Antifungal treatments containing clotrimazole, bifonazole, miconazole, miconazole nitrate, ketoconazole or terbinafine (excluding shampoos and nail treatments)
  • Benzoyl peroxide for acne treatment
  • Chloramphenicol eye drops
  • Decongestant nasal preparations containing oxymetazoline hydrochloride or xylometazoline hydrochloride
  • Hydrocortisone or hydrocortisone acetate
  • Hydrocortisone-antifungal combinations
  • Lignocaine (for superficial pain only, e.g. not for pain of injections)
  • Naphazoline eye drops
  • Nystatin oral drops
  • Potassium nitrate/fluoride desensitising toothpastes/gels
  • Povidone-iodine sore throat gargles
  • Sodium cromoglycate eye drops

When therapeutic equivalence data are required

For the following topically-applied ingredients or medicine categories, provide data to demonstrate therapeutic equivalence of the medicine to the Australian originator medicine:

  • Aciclovir
  • Anti-inflammatory sore throat preparations (excluding benzydamine hydrochloride lozenges)
  • Antidandruff shampoos containing imidazole antifungals or ciclopirox olamine as active ingredients
  • Antifungal nail treatments
  • Antiseptics/skin disinfectants
  • Corticosteroids (except hydrocortisone and hydrocortisone acetate; see also Specific OTC medicines)
  • Dithranol
  • Head lice preparations
  • Minoxidil
  • Non-steroidal anti-inflammatory medicines (NSAIDs)
  • Products containing glyceryl trinitrate (see also Specific OTC medicines)
If you are unsure about data requirements

The above lists are not exhaustive and the absence of any ingredient or medicine does not necessarily indicate that safety and efficacy data are, or are not, required - we may simply not have considered the ingredient or medicine in this regard (e.g. for recently down-scheduled ingredients). We will update these lists as further medicines are considered.

Contact OTC Medicines if you are unsure of data requirements.

Therapeutic equivalence data requirements

For data requirements, refer to Note for guidance on clinical requirements for locally applied, locally acting products containing known constituents (CPMP/EWP/239/95 final).

For topical solutions, refer also to Appendix II of Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev 1).

You will need to demonstrate therapeutic equivalence against the corresponding strength of the originator medicine as marketed in Australia. Refer to Choice of reference medicine.

2.3 Generic modified release dosage forms

Provide supporting data as described in the Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1), Section 6, Abridged application for modified release forms referring to a marketed modified release form.

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