A Year in European Variations Regulation

Pharma IQ

Variations, regardless of their simplicity, are still required to pass through a complex regulatory process for the products to remain authorised for sale on the market.

The process is essential to ensure that the drugs on the market remain safe and effective, yet the large number of member states and differing rules within the European Union has previously meant products were not falling under one single variations standard.

According to the European Commission (EC), "This lack of harmonisation had negative consequences in terms of the administrative burden, both for industry and national regulatory authorities, and the overall functioning of the internal market."

In a bid to combat this, the EC introduced changes designed to simplify the Variations Regulations. The changes took effect on January 1st 2010, yet early signs show pharmaceutical companies are struggling with the new provisions.

Key changes

Changes were made to the Commission Regulation (EC) No 1084/2003 and Commission Regulation (EC) No1085/2003 of  June 3rd 2003, with the intention of making the variations process simpler for those within the pharmaceutical industry.

The regulations relate to marketing authorisations for medicines for human use and animal use covered by both the competent authority of a member state and those which "fall in the scope of council regulation." 

Among the provisions laid out by the EC in the new regulations, was that the creation of definitions for each variation based on its level of risk should be laid down, which are to be regularly updated based on both scientific and technological advances.

Those changes which have the largest risk are to be scientifically assessed to the same standard as new marketing authorisations.  A work sharing scheme was recommended where one authority examines the variations on behalf of other concern.

In an effort to reduce the administrative burden, minor variations –  those classified as Type1A –are to be noted in an annual report and will not require prior approval.

However, this gave companies new responsibilities in relation to in-house management of minor variations.

Implementation of new regulations

The alterations to the variations regulations in the EU were adopted simultaneously by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK for all national variation applications.

Six months following the implementation of the rules for Type1A variations – those where the alterations are deemed to make minor or no changes on the safety or efficacy of a product- the MHRA reviewed the progress of the new system.

It found a "significant" number of Type1A regulations were rejected during the periods and many companies still needed to gain experience of the process.

The MHRA noted: "It is acknowledged that the system is still relatively new for some companies and that, depending upon how many Type IA variations a company may have had to manage during this period, experience is still being gained."

Some 30 percent of Type1A applications were found to be rejected over the period, however, the MHRA remains confident the system will prove effective.

"The deficiencies are generally of an administrative nature and therefore could be readily avoided and are easily resolvable in a resubmission," it stated.

Common reasons for the rejections included the form being incorrectly filled in, including a lack of a "clear present and proposed section", the wrong change code was used, which therefore meant the wrong checklist was supplied, and the exclusion of supporting documents.

Further issues covered the exclusion of the qualified person declaration, or a declaration which failed to cover all the companies involved in the variation, and a misunderstanding of the changes a Type1A application applied to.

The results show that there is still a way to go until the industry is capable of implementing the regulations to their full benefit, however, the MHRA believes this is likely to be something that comes over time.