Inhalation and nasal medicinal products are crucial in the treatment and management of allergy, asthma and chronic obstructive pulmonary disease (COPD) and must be of the highest quality. In November, EFA brought the patients’ perspective to two draft scientific guidelines under revision by the European Medicines Agency to reflect optimal pharmaceutical quality and the therapeutical equivalence of new and existing inhalation and nasal products.
EFA praises EMA’s efforts to ensure all inhalation and nasal medicinal products meet the highest quality standards and fully supports that the introduction of new products into the market respect quality and safety standards. We also welcome the increasing interest of pharmaceutical companies to develop technologies that aim to addressing personalised or unmet needs of patients. Innovative products might come with a better safety profile or a less burdensome treatment scheme, resulting in improved adherence to treatment and further enhancing their quality of life.
EFA patients recommendations on the draft guideline on the pharmaceutical quality of inhalation and nasal medicinal products
- Drug-device combination products – The legislation for combination products is currently fragmented in the EU. EFA believes that these products should be recognised as a separate category of medicinal products in the legislation. This would help streamline their development and ensure patient involvement throughout the life cycle of the product, which at the moment does not happen at all or only partially.
- Testing for real-world situations and usage- Test results of quality aspects should be valid in real-world situations and usage of the medicinal product, for example when traveling with the product or when using a spacer. In addition, instructions for safely and correctly handling the products and the robustness of their performance should also be tested throughout the lifecycle of the product.
- All patient profiles are addressed – Patients with different characteristics, diseases and disease severity may have different dose, usage and needs regarding the product. This should be reflected when checking product quality aspects. EFA made multiple comments to make sure all patients in the patient population concerned are represented when the quality of inhalation and nasal medicinal products is tested.
- Avoid potentially inflammatory excipients – The use potentially inflammatory excipients, like lactose, should be avoided as much as possible and, when used, allergen/intolerance and adverse reactions information should be clearly disclosed in the package leaflet.
- F-gases as excipients and research of novel excipients - Fluorinated greenhouse gases (F-gases) are often used in current metered-dose inhalers (MDIs) empowering effective inhalation, but they also impact the environment. EFA recommends novel excipients and propellants to be investigated on their therapeutic equivalent.
- A ml scale on all packages of liquid medicinal products – All manufacturers should be obliged to include an ml scale on the container of all liquid inhalation and nasal medicinal products, especially on opaque glass containers. This way, patients are aware at all times of how much product is left, leading to better self-management of their care and medicine use.
- Identifying last dose for pressurised metered dose inhalation products (pMDIs) – EMA should require that for all pMDIs, the last dose can be recognised by the patient to avoid an empty pMDI is continuously used without the patient knowing, which can have severe health implications.
EFA patients recommendations on the draft guideline on the requirements for showing therapeutical equivalence between new and existing orally inhaled products for asthma and COPD
Similarly to the the guidelines above, EFA highlighted the importance of representing all patient profiles when therapeutic equivalence is demonstrated and the need for real-world testing. In addition, EFA also submitted the following specific recommendations:
- A balance between patient safety and access to medical products – EMA should strike the right balance between patient safety and access to medicines through putting in place strict but relevant requirements for demonstrating therapeutic equivalence between a new/generic orally inhaled medicinal products and an orally inhaled medicinal product already on the market.
- Different product performance of different nebulisers – Since the performance of inhalation products for nebulisation varies greatly depending on the nebuliser used and mixture administered (dual and triple therapies), EFA recommends that all the nebulisers and mixtures mostly used with the reference inhalation product should be tested for therapeutic equivalence.
- Risk of medication error with reformulated dosage – in case the dosage strength of the test product must be changed in comparison to the reference product (e.g. when bioavailability of the test product is higher), it must be clarified by EMA how the potential risk of medication errors must be addressed and in case additional measures are needed, these should be tested with patients and validated.
- Extrapolation of results from adults to children – EFA stresses to be cautious when allowing to extrapolate results from studies on adults to adolescents (>12 years) and children (<12 years). Children are not small adults, so simple extrapolation to the pediatric population should not be allowed.
Next steps
You can find EFA’s full response to consultation on guideline on the requirements for showing therapeautical equivalence between new and existing orally inhaled products for asthma and COPD.
EMA will consider and look into the submitted comments by stakeholders and concerned individuals, before publishing the final guidelines. We hope they will take into account the needs and perspectives of patients with allergies, asthma and COPD as well as of their caregivers.