12th Conference in 2009

18 March 2010

Conference Report on the 12th European Conference on Active Pharmaceutical Ingredients

On 18 to 20 November 2009 APIC held its 12th European Conference on Active Pharmaceutical Ingredients in Venice in order to discuss topical GMP issues and regulatory requirements.

An important and intensively discussed subject was the supply chain integrity which was presented from industry and authority representatives. Tracing back the supply chain without gaps can be especially difficult if several distributors and/or repackers are been involved. The situation is even more complicated when the supply chain starts in Far Eastern countries like China and it can be a challenge to guarantee API quality and safety with regard to manufacturing standards over a longer period of time. Lionel Vornéry from the French Afssaps pointed out that there are considerable gaps within the current legal framework. He concluded that the standards are in place (Directive 2001/83/EC; EU GMP Guide), however enforcement is insufficient and API distribution chain actors like brokers are not captured.

Pharmaceutical companies are more and more aware of this challenge. Mary Oates from Pfizer explained the key elements for an ongoing oversight to ensure the entire supply chain integrity. One of them is that the quality systems of distributors must be evaluated and found to be acceptable.

Kristy Zielny from the FDA emphasised in her presentation the need of a risk based approach in supplier qualification and that management has to have an active role in continually evaluate the surveillance activities for robustness in accordance with risk. FDA will further increase focus on oversight and controls of the complete supply chain.

How does a QS help to secure the supply chain integrity? Francois Vandeweyer from Janssen Pharmaceutica explained the fundamentals of successful Quality Supply Chain System and emphasised the importance of knowledge management and continuous improvement over the whole chain.

According to Bernd Schade, Bayer Healthcare, another key element for ensuring the integrity of the supply chain is the establishment of regular governmental inspections in particular in Far East. He concluded that more of these inspections would further increase the safety of imported APIs and support the GMP surveillance of local authorities. Rebecca Wang from Bayer Healthcare, Beijing confirmed this statement. She explained the role of the SFDA and other relevant Chinese authorities and gave recommendations on how to source APIs from Chinese manufacturers.

Charles Hu, BimSifram Group, presented some ideas and criteria which would contribute to increase the safety of imported APIs. He stated that a EDMF and a CEP respectively can be considered as an API "passport" and emphasised the necessity of a united EU API Inspection and Certification Programme.

The Status of the International API Inspection Pilot Programme and other international perspectives in GMP were the topics of the presentation given by Olivier Gross, EMA. This Pilot Programme should result in a better use of International inspectional resources and a better coordination, collaboration and information between authorities. An important element of the Programme is the exchange of information by gathering and sharing more data on site inspections planning.

In the following the further highlights of the conference are outlined.

The European Generic Medicines Association (EGA) strongly supports an enhanced supervision of global supply chains by EU authorities, EDQM and industry. According to Julie Maréchal-Jamil, EGA, the feasibility of mandatory EU API GMP inspections needs to be established prior to any legal change.

Falsified Medicines are a serious threat of public health. APIC's president, Chris Oldenhof, DSM, illustrated the magnitude of the API problem and where rogue APIs are coming from. He emphasised the necessity for inspection of non-EU API manufacturing sites. The total number of these sites is estimated by APIC to be in the range of 500.

Another key topic at the conference was "Quality by Design" (QbD) and Q8, Q9, Q10 within the ICH framework. In his lecture on the status of current FDA quality initiatives Dr Moheb Nasr explained the status of implementation of QbD concepts and demonstrated how the FDA considers QbD applications.
A status update and the content of the new Variations Regulation (legally binding since 1 January 2010) and the supporting guidelines was given by Maia Figuerola-Santos, EU Commission. She presented an overview of the main aspects of the regulation and the contents of the guidelines and summarised the main issues from the public consultation about the guidelines.

What are the benefits of the new EU variations regulation and the supporting guidelines for the API industry? In her detailed consideration on the contents of the guidelines Hilde Vanneste, Janssen Pharmaceutica explained the particularities of different changes and types of variations in the light of the new regulation.

In order to obtain a "Certificate of Suitability" (CEP), which confirms that the Ph. Eur. Monograph is suitable for controlling the quality of the active ingredient, some of the API manufacturers also have to undergo inspections co-ordinated by the European Directorate for the Quality of Medicines and Health Care (EDQM). In her presentation on EDQM's inspection programme Hélène Bruguera gave an update of this programme and the evaluation of applications.
The API industry has a very positive view of EDQM's CEP procedure which was confirmed in his lecture by Jan Smeets, DSM. He highlighted the advantages of the procedure which consist of e.g. less administrative burden compared to the EDMF procedure and a central review/approval.

In April 2008 the ICH published the final concept paper "Q11: Development and Manufacture of Drug Substances (chemical entities and biotechnological/biological entities)". Step 2 (Confirmation of consensus) is scheduled mid-2010. Seppe de Gelas from Amgen explained the benefits of applying ICH Q11 principles. He demonstrated how the regulatory evaluation process for authorities will be facilitated by this guideline.

Once more the conference offered a wealth of new information to the delegates. The high quality of the lectures given by key representatives from both industry and authorities combined with the willingness to discuss matters in all openness, resulted in this event again contributing much to a further increase in mutual understanding between the API industry and the supervisory and registration authorities. Many of the new developments reported at this conference are snapshots, so we all looking forward to what the 13th APIC Conference, to be held in Barcelona from 27 to 29 October 2010, will bring.