The new Annex 16 is coming into Force

The new Annex 16 "Certification by a Qualified Person and Batch Release" will become effective as of 15 April 2016.

It is centrally pointed out that the main duty of a Qualified Person (QP) is the certification of batches. In this context, the QP must personally ensure that the responsibilities listed under Chapter 1.6 are fulfilled. Chapter 1.7 lists many other responsibilities to be guaranteed by the QP. However the related activities can be delegated and the QP can rely on the respective quality management systems. Yet, the "QP should have on-going assurance that this reliance is well founded" (1.7). The 21 responsibilites listed include amongst others:

• The starting materials used comply with the requirements and the supply chain is known and under control.
• The necessary audits have been carried out and the audit reports are available.
• The manufacturing processes and testing methods are validated and in accordance with the marketing authorisation.
• Changes have been assessed and completed accordingly.

In this context, it is important to mention that the Annex clearly highlights that the overall responsibility (safety, quality and efficacy) for a medicinal product lies with the marketing authorization holder (MAH). "However, the QP is responsible for ensuring that each individual batch has been manufactured and checked (…) in accordance with the requirements of the marketing authorisation (MA) and with Good Manufacturing Practice (GMP)" (see general principles).

In cases where the QP has to rely on the functioning QM system of another site, the QP must ensure that a documented review and permission of audit reports by third parties is available.

Another important section clarifies the role of the QP with regard to deviations and includes a few elements from EMA's position paper on QP Discretion (published in February 2006 and updated in January 2008). Chapter 3 of the new Annex describes the "handling of unexpected deviations". A batch with an unexpected deviation concerning the manufacturing process may be certified if the result of a risk analysis performed shows that "the potential impact of the deviation on quality, safety or efficacy of the batch(es) concerned and conclusion that the impact is negligible." In cases where a deviation concerns specification defined in the marketing authorisation as essential for the release (OOS; out of specification), the QP will still have no scope left.

During the consultation phase, interest groups have expressed their concerns with regard to the sampling of imported products. Now, the new Annex 16 makes clear that "samples may either be taken after arrival in the EU, or be taken at the manufacturing site in the third in accordance with a technically justified approach which is documented within the company's quality system. (…) Any samples taken outside the EU should be shipped under equivalent transport conditions as the batch that they represent." 

Regarding any requirements on import, the new Annex 16 "Certification by a Qualified Person and Batch Release" has been kept relatively short. Those requirements will probably be set in the new Annex 21.