PAEDIATRIC USE - PROPOSED REGULATION
As we get older, we become increasingly attractive - to the pharmaceutical industry at least! Children are quite unattractive to R and D companies - partly because there are far fewer of them than adults, but also they tend to be healthier. Many diseases tend not to affect children. As a mother of two, I am very glad of this. I am quite happy that they should be ignorant, for the time being, that life is a progression towards death! One of the downsides is that since children do not represent a big enough market, clinical trials are often not carried out in relation to paediatric use. Paediatric doctors have to prescribe medicines for children which have not been evaluated in children. Currently more than 50% of medicines used in children have not been tested and not authorised for use in children. The doctor's decision is not evidence-based. This carries risks : it is estimated that the fifth largest cause of death of hospitalised US adults is ADRs, and there is a greater proportion of ADRs in relation to off-label use. It is inevitable, given the lack of clinical trials in relation to children, and off-label use, there is an increased risk of ADRs. And children are different from adults. They cannot swallow in quite the same way and there are differences in preferred mechanisms of delivery.
At the moment, pharmaceutical companies are free to choose what medicines to develop, register and sell. Of course, they want a return on their investment. For many medicines, market forces alone are not sufficient to encourage the investment needed to carry out clinical trials for paediatric use.
A proposed new regulation on medicines for paediatric use would change all that. On 10th March the Council adopted a common position in relation to the Commission's proposal to adopt a regulation relating to medicinal products with paediatric use. In large measure, this echoes the Commission's original proposal made in October 2004. The draft regulation follows the US, which introduced special incentives for paediatrics some years ago. Generally, it seems to be thought that those changes have been beneficial.
When, as seems likely, the new regulation comes into force, pharmaceutical companies will be required, in certain circumstances, to ensure that data is generated in order to authorise certain medicines for use in children. They will have to carry out a paediatric investigation plan ("PIP"), i.e. an R&D programme aimed at ensuring that necessary data is generated to authorise medicines for use in children if there is a potential therapeutic benefit to children, mand taking into account that requirements for studies in children should not delay the authorisation of medicines for adults.
Data resulting from the PIP is required at the time that a marketing authorisation is made. There is a system of waivers from the requirement for a PIP for medicines that are unlikely to benefit children. We cannot yet know how broadly this will be applied. Clearly, medicines for Alzheimers or Late Onset Diabetes need not be developed for children - but what about products for Heart Disease? I am sure that this will need clarification.
There are systems of deferrals from the requirement for data to ensure that medicines are tested in children only when it is safe to do so and to prevent the delay of authorisation of medicines for adults.
The costs of carrying out an R&D programme in children will be high, and as compensation for the extra costs involved, and an incentive for more R&D, companies are to be granted a six month extension of their monopoly in the form of a six month extension to SPCs across the whole product range whether or not the paediatric indication is granted. It is a reward for conducting studies in children, rather than for demonstrating that the product is safe and effective in children. In the case of blockbuster drugs, the benefit to the patent holder will far outweigh the costs. It is estimated that overall, the cost of carrying out trials in children will be around €4,000,000 per medicine. Administrative costs are on top of these. Profits are estimated at €0.8m -0.9m per product.
For orphan medicines there is an incentive of two additional years of market exclusivity to the existing ten years awarded under the EU Orphan Regulations.
The draft regulation contemplates:
It is not yet clear how the last would work. Clearly, each product which is to be used with children must be tested, and at least for patented products, only one company will be interested in each such drug. Obviously, one does not want children to be tested on a multiplicity of drugs, and if a system can be introduced which works well for children, then perhaps a similar set up could benefit other patient populations.
Of course, the extension to the SPC, and extension to market exclusivity for orphan drugs will delay marketing of generic medicines. Poland, in particular, has objected to the regulation, voting against it because the delay of generic products would increase its healthcare bill. The EGMA has argued that the six month extension should not be applied to blockbuster drugs, estimating that an extension to blockbusters would generate up to €20 billion in additional costs to healthcare systems. The EU Geriatric Medicine Society points out that the elderly population is increasing, yet most medicines haven't been tested on older populations. I am not quite sure whether this is intended to persuade the authorities that clinical testing in children is not necessary, or to encourage the adoption in a similar regime for the elderly.
In some cases, the availability of an extension to an SPC could be a disproportionate incentive, and leads to companies seeking to do new research simply to enhance their monopolies. It would be very interesting to consider such activities from the point of view of competition law.
In order to provide an incentive for off-patent medicines, a new type of marketing authorisation, the Paediatric Use Marketing Authorisation (PUMA) is proposed. This is specifically for products developed exclusively for use in children and the company developing data benefits from data protection relating to paediatric use.
Ten years protection is proposed. This could make the development of paediatric data for generic products extremely valuable, and generic companies might like to become involved with this. An application for a PUMA requires the submission of data necessary to establish safety, quality and efficacy specifically in children, including any specific data needed to support an appropriate strength, pharmaceutical form or route of administration of the product, collected in accordance with the PIP. These data can be derived from publicly available or new studies. The application can refer to data contained in the dossier of an authorised product.
In considering the proposed regulation, the balance of public health issues should be taken into account. There is a benefit in being able to establish, evidentially, that medicines used for children are safe and, costs to the healthcare system will be increased and generic companies will lose profit. Is a balance correct? Could more be done, in order to avoid unnecessary trials (and the extensions which go with them) by considering the nature of adverse effects. There may be general principles which are applicable to children and which could simplify matters.
The current status is that the Council of Ministers has backed the proposed regulation, adopting a common position on the 10th March, and the draft proposal will now proceed to a second reading in the European Parliament, and could become law next year. Watch out for it! And call me if you wo0uld liken advice on this or other matters affecting you.
Anna McKay, March 2007
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