Starting debate: EMA says rules on API materials need clarification

22-Oct-2014 - Last updated on 23-Oct-2014 at 14:14 GMT

When does API production start? EMA says clarification needed

Drugmakers’ clashes with regulators over the suitability of API starting materials suggest ICH Q11 is open to interpretation and that clarification is needed according to the EMA.

As the name implies, “starting materials” are considered the first substance used in the production of an active pharmaceutical ingredient (API), which means they need to be produced in accordance with good manufacturing practice (GMP) standards.

However, while the terms are clear, the problem according to the European Medicines Agency (EMA) is that drugmakers and regulators often disagree on what constitutes a starting material as a result of flexibility built into ICH Q11 guidelines.

The EMA made the comments in a concept paper issued earlier this month that it said is designed to make clear what information drugmakers need to provide to justify use of a particular starting material.

Key topics covered in the concept paper include the production of APIs using complex, custom-made starting materials which, while allowing manufacturers to shorten synthesis routes, increase risk according to the Agency.

“The use of external sources for any steps in a manufacturing process may lead to a higher degree of risk to quality of the active substance than would be expected were the full manufacturing process to be carried out by the applicant or a single active substance manufacturer alone.”

The EMA also tries to address Active Substance Master Files (ASMF), explaining that data submitted to justify selection of a starting material “is often insufficient to allow adequate assessment of suitability.”

The EMA has had the most experience of ICH Q11 of all the major global regulatory bodies.

The London, UK-headquartered organisation adopted the scheme shortly after its release in May 2012, six months ahead of the US Food and Drug Administration (FDA). Japan’s Ministry of Health, Labor and Welfare (MHLW) followed suit in July this year.