IPEC e-newsletter - Excipients Insight September 2017 - 19-09-17



Dear colleagues,

A warm welcome back after the summer break. We now enter that period which takes us, all too quickly it seems, to the end of another year. September in itself is extremely busy with several committee activities happening and a meeting of the IPEC Europe Board, while the association will be present at two major events - namely the APV/IPEC Europe Excipient Conference in Berlin, (19-20 September 2017) and Powtech 2017 in Nuremburg on 26-28 September. More details are available at info@ipec-europe.org of course, but I did want to mention that we always welcome members' inputs to our various events. And for those of you who may be attending either of the conferences in Germany, please stop by at our stand. There is no substitute for face-to-face contact, surely the best way to find out from you directly what you think about IPEC Europe's current and future direction.

In this edition, we introduce our latest task force to be created, that is, to look at the contact materials used for excipient packaging. As ever, what does and doesn't apply to excipients in the complicated world in which they exist, is not clear. The diverse sources of excipients include several industries such as chemicals and foods, where their own regulations drive considerations when a material is used for pharmaceutical purposes. One of the best things that we can do as part of our mission is to help provide some direction as to what is reasonable which will satisfy regulator and customer alike. The need for this initiative started from enquiries from our membership, so please keep your questions coming so we can be sure we best represent what’s important to you!

Another area where there has been a lot of activity lately relates to the European Food Safety Agency’s (EFSA) – see our article here – and this edition also provides information on antioxidants which also may be used as excipients and alerts us to the fact that when it comes to excipients, we need to always think laterally so we don't fail to detect matters of importance.

So, I will leave you now to enjoy this edition and here’s hoping some of us will get the opportunity to meet in Germany!


Frithjof Holtz

Chair of IPEC Europe



IPEC Federation sets out its plans for the coming year

In July, representatives of the IPEC Federation met in Beijing, China, to convene a board meeting, attend a workshop with the country's Centre for Drug Evaluation, CFDA, and participate in ExcipientFest Asia as a co-sponsor of the event.

The packed week provided an opportunity for the Federation to review progress with its work programme and objectives for the coming year to provide "a more refined focus," according to Patricia Rafidison, President of the organisation.

Rafidison told Excipients Insight that some projects – including preparing harmonised position papers on data integrity, atypical actives and supply chain security – have been given priority, along with risk assessment, projects on the recently-revised IPEC-PQG Good Manufacturing Practice (GMP) guide and the IPEC-Americas Excipient Information Package (EIP), and monitoring the regulatory situation for excipients in China, such as the revision of the Chinese Pharmacopoeia and new Bundling Review process.

The GMP guide has now been launched by the Federation, and work will now start to transform it into a 'how to' document aligned with ANSI/IPEC/NSF and EXCiPACT standards and in an ISO format, while the EIP will be developed into an IPEC Federation document. Additional details on the Federation work plan are available from the secretariat.

On the topic of supply chain security, work is aimed at developing strategies for performing excipient assessment and management in collaboration with other industry organisations, such as EXCiPACT, and ANSI-NSF.

Interactions with regulators continues to be high on the agenda for the Federation, with the overarching aim of encouraging scientific, risk-based global regulatory standards for excipients. The fantastic work carried out by IPEC teams on ICH Q3D is a testament to the benefits of that high-level engagement with regulatory bodies, said Rafidison.

"It's so important to give a voice to excipients, and to provide a reality check where needed," she asserted. To that end, the relationship with the Pharmacopoeial Discussion Group (PDG) continues to be fruitful, while the Federation is also committed to working towards the development of its own harmonised voluntary guidance.

The annual meeting between IPEC and the PDG took place this month – with discussion on topics including cellulosics, silicon dioxide and ICH Q3D - and a report will follow in the next edition of Excipients Insight.

The Federation's international expansion is also progressing well, and is now starting to develop a "truly global reach", said Rafidison.

IPEC India – which has three seminars planned for 2017 to raise awareness of the Association and excipient matters - is "building up nicely", she noted, and thanks to strenuous efforts by IPEC-Americas considerable progress is being made towards setting up partnerships with associations in South America, with training sessions being run in Brazil and Argentina and additional seminars planned in the coming months.

There are also plans to widen the Federation network even further with collaborations planned with additional Asian countries.

Communication is also a top priority, and a key decision taken at the Board meeting is to organise a global IPEC conference in 2019 bringing together all five regional associations.

"As regulators continue to support regional regulations, it is paramount that a risk-based approach continues to be integrated in excipient regulatory assessment and compliance," said Rafidison.

"Setting up a global conference will allow IPEC to promote the importance of excipient quality and safety, educate industry and regulators about excipients specificity globally, and increase IPEC visibility by sharing key objectives, as well as tools and guidelines developed over the years to support excipients compliance."

The IPEC Federation will next meet face-to-face for its Annual General Assembly in Bordeaux, France on 30-31 January 2018.



IPEC Europe sets up contact packaging taskforce

Increasingly, excipient suppliers are receiving questions about primary packaging materials (PPM) from customers as to whether PPMs for excipients meet pharma and other industry requirements. An example was quoted related to polyethylene bags and did they meet the European Pharmacopoeia (Ph. Eur.) requirements for olefins.

As there is no formal position with IPEC on this topic, a task force has been convened to review available information to help IPEC members understand where excipients and the primary containers used to supply them ‘sit’ in this arena. If you would like to get involved in this important project please let the IPEC Europe secretariat know.




EXCiPACT update

Despite the traditionally quiet summer period, EXCiPACT has nevertheless added a number of new certificates, including Colorcon's Indianapolis site and Hangzhou Rossen Lipids Technology site in Zhejiang Province, raising its tally to 52 at the end of August from 55 at the end of July.

An EXCiPACT China Workshop organised by the organization's local consultant on 14 July in Shanghai was a success, with about 40 quality attendees from Chinese pharma excipients suppliers, users and regulators as well as our local certification bodies SGS and BV and IPEC China. Sarbary Roy, EXCiPACT's vice-president, gave two presentations.

In mid-August the organization held a quarterly update meeting with its members



IPEC Europe welcomes new intern Ilias Grampas

IPEC Europe's secretariat is pleased to welcome Ilias Grampas, who has joined IPEC Europe for a six-month internship programme. Ilias is providing support for the secretariat with communication activities, including a project to redesign our website and setting up a dedicated event platform, refining the association's social media presence and other activities.

A graduate of the University of Macedonia in Greece, Ilias completed a first degree in International and European Studies and followed that with a Master's degree in Crisis and Security Management at Leiden University in the Netherlands. A native Greek speaker, he is also competent in English, German and French. Prior to joining IPEC Europe he worked as a communications assistant at the United Nations Environment Programme in Brussels.

"It is a pleasure to join IPEC Europe, working in the field of communications, where I can brind immediate strategic value and develop my current skill-set further," he said.



IPEC Europe calendar

Group Q2/Q3 2017
IPEC Europe Board 26 September - Nuremberg / 28 November - Brussels
GDP Committee TBC
Pharmacopoeial Review & Harmonisation TBC
Quality/Regulatory Affairs 28 September - Brussels / 16 November - Darmstadt



EFSA review on food additives raises pharma questions

The European Food Safety Agency's (EFSA) risk-assessment review of certain food additives continues, with the agency completing its re-evaluation of food colourants in July having assessed 41 colours. As a result of this work, the maximum levels of three colours (E 104, E 110, E 124) were lowered and the colour Red 2G (E 128) was removed from the market.

IPEC Europe has been monitoring the EFSA activities to see whether these have any impact on the use of those same materials in pharmaceuticals. We recently shared the planned actions related to the use of iron oxides (E172), whereby EFSA has requested more safety data to support its continued use as a food additive. If EFSA removed E172 from the EU food additives list, legislation governing colouring matters which may be added to medicinal products (Directive 2009/35/EC) could also be affected which would be a major issue.  As it stands E172 is not on the EFSA's tentative work programme for 2017.

On 24 November, EFSA will host a one-day workshop on the status of the EU re-evaluation programme of food additives. The day before, observers will have the opportunity to attend the open plenary of the Authority’s Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS).



Antioxidant excipients and health claims; consultation

The European Food Safety Authority (EFSA) has just completed a consultation period on draft guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. The news is notable as antioxidants include a number of compounds that are also used as excipients.

Antioxidant excipients include substances such as ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), butylated hydroxyanisole and butylated hydroxytolune, and are used in pharmaceutical, nutritional and cosmetic products to protect them from oxidative degradation, for example to improve the shelf-life of medicines and prevent oil-based products turning rancid.

The consultation considers claimed effects which are considered to be beneficial physiological effects, and discusses the kinds of intervention studies which can provide evidence for the scientific substantiation of specific claims.

More information is available here.



Strengthening EU-US cooperation in medicine inspections

The US Food and Drug Administration (FDA) has agreed to share full inspection reports with the European Commission and European Medicines Agency (EMA).

The parties have signed a confidentiality commitment that allows the US regulator to share non-public and commercially confidential information, including trade secret information relating to medicine inspections with EU regulators.

"This confidentiality commitment is a milestone in the ongoing implementation of the mutual recognition of inspections of medicine manufacturers and it aims to strengthen the EU-US relationship," said the Commission in a statement.

"Ultimately it will contribute to a more efficient use of inspection resources by regulators for the protection of human and animal health."

The EU and the US have had confidentiality arrangements in place since 2003, allowing for the exchange of confidential information as part of their regulatory and scientific processes. However, complete exchange of information was not possible under these arrangements.

The new confidentiality commitment formally recognises that FDA's EU counterparts have the authority and demonstrated ability to protect the relevant information. This step now allows the sharing of full inspection reports, allowing regulators to make decisions based on findings in each other’s inspection reports and to make better use of their inspection resources to focus on manufacturing sites of higher risk.



Excipients used to stabilise new viral vector for gene therapy

Excipients have been used to stabilise viruses used to transfer genetic sequences into cells – for example for gene therapy – in a development that could make an improved vector suitable for development as biologic therapies.

The research by scientists at Oklahoma State and Kansas Universities in the US is focusing on adenovirus, and specifically a form of the virus known as "fibreless adenovirus" in which proteins found in the organism that contribute to undesirable characteristics such as immune stimulation are stripped out. Removing those proteins also allow modifications to the virus to improve its therapeutic characteristics

Adenoviral vectors have featured prominently in gene therapy experiments – used in upwards of 400 clinical trials – but have been associated with side effects, including the death of a patient enrolled in a gene transfer trial at the University of Pennsylvania in 1999. Fibreless versions of these viruses have been proposed as an alternative, but removing the fibre leads to serious stability issues.

"There is clearly a need to stabilize fibreless adenovirus so that it can serve as a platform for improved adenovirus-based therapies," write the researchers in the Journal of Pharmaceutical Sciences. "Currently, a stable formulation of fibreless adenovirus has not been described."

The team screened various excipients to find candidates that could stabilize the fibreless adenovirus by measuring their ability to improve thermal; stability and prevent aggregation – which leads to a loss of protein activity - and improve the retention of their biological activity. The best excipients were found to be the nonionic surfactant Pluronic F-68 and glycine.

"The work presented here demonstrates that it is possible to enhance the stability of the fibreless adenovirus, which can result in a longer shelf life and, consequently, more consistency in therapeutic efficacy," conclude the researchers.

"We showed that a simple formulation, such as addition of a single excipient, can significantly increase the particle stability and retain the biological activity of the virus."



Recommended reading

Salvagers of solubility

High throughput excipient discovery looks set to boost oral bioavailability. A collaboration between the Dow Chemical Company and University of Minnesota has yielded a new method allowing the production of excipients that triple the oral bioavailability of drugs, when compared with commercial excipients.

The Medicine Maker

Pharmaceuticals, printers and paintballs: when variability in excipient quality is and isn’t acceptable

Regardless of whether it’s prescription or over-the-counter, the ingredients on a drug product label typically include one, maybe two, active pharmaceutical ingredients (APIs). The rest of the list is comprised of “inactive” ingredients (excipients) which in reality are far from inactive. Their functions range from helping to guarantee the stability and bioavailability of the API to the drug product’s manufacturability to its texture and taste. Because of the multiple roles they play in drug product formulations, excipient quality is as important as that of the API, so standards are needed to ensure their purity and reliability.

USP Quality Matters (video)

Recent developments regarding a Novel Excipient Qualification process

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) and the International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) are working toward accelerating excipient innovation and ways to bring forth novel excipients with enhanced functionality that improve drug delivery and manufacturability (e.g., continuous manufacture) and that focus more on the needs of special populations (e.g., pediatrics). This collaboration led to a Critical Path Initiative Meeting (CPIM) with the FDA on March 10 to discuss developing an independent Novel Excipient Qualification process that encourages the development of innovative novel excipients and their use.

Tablets & Capsules

Indian Gov outlines plan to favour drugs containing locally made APIs

Price controls and procurement programmes would favour drugs containing locally-made APIs under a Government proposal designed to reduce India's reliance on imported ingredients and intermediates.




Download IPEC Europe guides

All of IPEC's guides are available for free download via our website. Follow the links below to make your selection. 

  • 2017 The Joint IPEC-PQG Good Manufacturing Practices Guideline - Updated version
    Download PDF
  • 2017 The IPEC Good Distribution Practices Guideline - Updated version
    Download PDF
  • 2016 IPEC Europe 'How-To' document on Risk Assessment
    Download PDF
  • 2014 The IPEC Glossary of Terms
    Download PDF
  • 2014 The IPEC Significant Change Guide: Third revision
    Download PDF
  • 2013 The IPEC Certificate of Analysis Guide
    Download PDF
  • 2012 IPEC Excipient Information Package (EIP): Template & User guide
    Download Word or PDF
  • 2011 The IPEC Good Distribution Practices Audit Guideline
    Download Word or PDF
  • 2010 The IPEC Excipient Stability Program Guide
    Download PDF
  • 2009 IPEC Quality Agreement Guide & Template
    Download Word or PDF
  • 2008 Qualification of Excipients for Pharmaceutical Use Download (Word) or (PDF)
    Download Word or PDF
  • 2008 The IPEC-PQG GMP Audit Guideline
    Download Word or PDF
  • 2008 The IPEC GDP Audit Guideline
    Download Word or PDF



Events calendar

Here is a round-up of forthcoming events of interest to suppliers and users of excipients. Please let the IPEC Europe Secretariat know if we've missed one.

APV/IPEC Europe Excipient Conference 2017 - an update on regulatory and application developments
Berlin, Germany - 19-20 September 2017
More information here.

Conference on the place of the Certification Procedure in the global regulatory environment
Prague, Czech Republic - 19-20 September 2017
More information here.

9th Conference of the European Paediatric Formulation Initiative
Warsaw, Poland - 19-21 September
More information here.

PowTech 2017
Nuremberg, Germany - 26-28 September 2017
More information here.

20th APIC/CEFIC European Conference on active pharmaceutical ingredients
Berlin, Germany - 25-27 October
More information here.

11th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology
Granada, Spain - 19-22 March, 2018
More information here.

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