IPEC e-newsletter - Excipients Insight October 2017 - 16-10-17



Dear readers,
Our October edition of Excipients Insight is rather a bumper one! There’s a lot happening not least in the European regulatory environment, with seemingly many new revisions of legislation and guidance related to medicinal products. We all know how hard it is to keep track of everything and we very much hope that the updates in this month’s publication help you with that goal. This leads me nicely to mention the survey you’ll find in this edition. It’s one of our objectives this year to see how we can make Excipients Insight better - does it meet your current needs? And what of the future? In which direction would you like to see our primary communication tool progress? I know I’m always asking things of you but I hope that you can find time to take this short survey. It will really help us to set some targets so I thank you in advance for sharing your thoughts and ideas with us.

But back to regulatory news. The EC and EMA have published Revised Labelling Guidelines for certain excipients so that’s a ‘must see’ for many members. So far only the annex has been revised, with the main text still to be updated. IPEC Europe has submitted comments on the revision and we will update the membership when there are further developments to report.  Meanwhile, there are other updates on GMP for commercial and investigatory products and also news of revisions to the Turkish GMPs, to align them more closely with PIC/S and so EU GMP requirements. Turkey has a robust inspection process in place and as one of the chapters updated in 7. Materials Management which includes the evaluation of suppliers, it could well result in more inspection focus on excipients, so take note!

There’s a lot to report on IPEC activities, too. With the APV/IPEC conference in Berlin, exhibiting and presenting at Powtech in Nuremberg, and IPEC Federation meetings with the Pharmacopoeia Discussion Group and China regulators, I think 2017 certainly represents an improvement in our collective outreach. We have to ‘speculate to accumulate’ and here’s hoping this translates into new members and very importantly, helps to achieve that part of our vision to promote and achieve worldwide acceptance and use of the IPEC developed guidelines. I would like to highlight the article on the longstanding certification process in Japan, namely the GMP Auditing Board for Pharmaceutical Excipients (GAB). Several members have asked for more information on this programme which will hopefully be of interest to many more. At Nuremberg, the IPEC Europe Board held its third face-to-face meeting this year which will be reported in the November edition. But from here on to the end of this year, we’re focusing on the next stage of our Agenda 2020 and the 2018 objectives to achieve that. So I leave you with another request, to revisit this document, and don’t hesitate to contribute any of your own views to develop the next stage of our journey!


Frithjof Holtz

Chair of IPEC Europe



Highlights of APV/IPEC Europe Excipient Conference 2017

The APV/IPEC Europe Excipient Conference 2017 was held on 19-20 September in Berlin, Germany, providing the usual high-quality insights into regulatory developments in the excipient field and their application.

The well-attended event got underway with three parallel workshops on issues that are of particular importance at present in the excipients arena.

Christa Farber of Staatl. Gewerbeaufsichstsamt Hannover and Eberhard Kwiatkowski of PharmAdvantageIT covered the topic of data integrity, examining how this concept can be applied to the excipient manufacture and supply chain. Astrid Stockrahm of DFE Pharma tackled quality agreements, showing how IPEC’s forthcoming QA guide and template can ease the relationship between excipient supplier and pharmaceutical manufacturer. Rounding out the trio was a workshop on stability testing of excipients by Tanja Natterer of Aug. Hedinger GmbH & Co, which showed how the IPEC Excipient Stability Guide can help in the design of an effective testing programme.

Thomas Storm of Novartis kicked off the conference proceedings on the second day, with a presentation on the challenges of multi-compendial compliance for excipients, reviewing the status of pharmacopoeial harmonisation as well as requirement beyond pharmacopoeial compliance. He said that compliance requires continuing efforts in development and routine quality assurance and unfortunately also redundant testing as the large majority of excipient monographs are not harmonised and there are incompatible standards or specifications between regions. The harmonisation effort is a successful process but slow, and industry “would like to see more of it, and faster,” he said, noting that functionality-related characteristics are becoming more of a focus.

The topic of extractables and leachables from excipient storage containers, and their potential as a source of impurities, was tackled by Steven Watt of A&M StabTest GmbH, who noted that while this has been considered in finished drug products there does not appear to be any direct guideline on this as it applies to excipients. He described leachable/extraction studies and workflows used in finished products and described how these concepts could be applied to excipients in storage containers

Jean-Claude Soule of Eli Lilly covered quality audits and how they can be used to ensure excipient supply chain security, reviewing supply chain vulnerabilities, regulatory expectations and guidelines for quality management system audits laid down in ISO 19011:2002. He described the various warning signals that can be looked for during an audit advised on ways to handle a refused audit, concluding that a combination of auditing, testing and pedigree is the best way to reduce risk. He noted that the quality agreement between an excipient supplier and user must describe all the companies involved from raw materials to finished excipient.

Speaking on behalf of the IPEC Federation, Frank Milek of Aug. Hedinger GmbH & Co examined the challenges posed by the complexity of the excipient supply chain, focusing on a string of events in which adulterated excipients have resulted in fatalities since the 1990s, the regulatory response to those tragedies, and showing how tools such as the recently-revised IPEC GDP guide can be deployed to ensure the safe supply of excipients. He also described how the IPEC Federation can facilitate that vision.  The organization’s position as the umbrella association for IPECs in the Americas, Europe, Japan, China and India put it in an important position to achieve this goal, he said, through measures such as the development and adoption of harmonised guidance and risk-based global regulatory standards, and serving as a reliable and credible source if information relating to excipients.

A regulatory perspective on the implementation of ICH Q3D on elemental impurities – which applies to marketed products including new mutual recognition applications of already approved products from December - was delivered by Bruno Spieldenner of the European Directorate on the Quality of Medicines and Healthcare (EDQM). He discussed the implementation of ICH Q3D in the context of the European Pharmacopoeia (Ph. Eur.) general text, chapters, methods and monographs, and reviewed approaches for specific elemental impurities tests, calling for additional expertise and support – especially from manufacturers – to revise and maintain those tests. He also took some time to review the implementation of the new requirements in the certification procedure, referring to a policy document adopted by EDQM in August.

Nikola Matic of Kline & Co broadened out the discussion with a presentation on the global excipients market, and particular those used in oral solid dosage forms which remains the most important sector for excipient suppliers in terms of size and while fragmented had an estimated value of $4bn in 2016, with a volume consumption of around 641,000 tonnes. The market is expected to grow at a healthy 5.6% rate to 2021, driven by an expanding overall pharma and particularly the generic drug market, the increasing complexity and low bioavailability of new active pharmaceutical ingredients (APIs) that need functional excipients, and the development of improved excipient grades for new applications.

Johann Philipp Hebestreit of BASF began the technical part of the conference programme with a presentation on preventing alcohol-induced dose dumping (ADD), the problem of unintended and excessive release of a pharmacologically-active ingredient as a result of alcohol consumption, which is known to be an issue with some sustained-release formulations. With the use of case studies, he showed how formulations can be at risk of ADD, and described how it can be avoided through the use of excipients such as BASF’s polymer-based Kollidon SR.

Laura de Miguel of Omya International took on another technical topic, looking at filler-binder excipients for direct compression and particularly co-processed excipients – new or novel combinations of established excipients – that in this setting can improve characteristics such as compactability, flowability and friability. With regulatory pathways to approval of novel excipients challenging, co-processed excipients help improve finished product characteristics, delivering a marketing advantage and potentially extending a product’s life cycle.

Excipients are also an important enabler of transdermal drug delivery systems (TDDS), and Sebastian Braun of Tesa Labtec GmbH broke down the various components of a TDDS, and showed how excipients fit into the structure of these products. He also looked at the documentation requirements involved if a drug master file (DMF) is available or not, and discussed the impact of the EU guideline on formalised excipient risk assessment in the context of TDDS development.

The technical programme also included a presentation by Kofi Asare-Addo from the University of Huddersfield School of Applied Sciences on advanced imaging in pharmaceutical materials, covering technologies such as infinite focus microscopy and how they can be applied to the design of robust formulations for drug delivery. Finally, Mats Hertel of Christian-Albrechts-Universitat Pharmazeutisches Institut looked at the use of excipients as drug carriers for pulmonary drug delivery, including the importance of matching the carrier to the device and optimal blending practices.

The next APV/IPEC Europe Excipient Conference is scheduled to take place on 18-19 September 2018.



Quality & Regulatory Affairs Committee (QRAC) update

Twelve Quality & Regulatory Affairs Committee  (QRAC) members met in Brussels on 28 September, with many more joining online, to review and progress the many initiatives under the responsibility of this group.  One of the tasks which was accomplished was to finalise a tracking tool for all on-going activities, identifying those projects which are active and others which only require monitoring at this stage. The grid will be posted on the committee’s site in the members’ area and will include those activities which are not directly managed by IPEC Europe’s QRAC but relate to its remit. An example would be ICHQ3D efforts on elemental impurities, which are led by a task force but one the QRAC’s team will keep actions and outcomes on its ‘radar’.

Of the main topics discussed, some time was devoted to sharing experiences related to the introduction of the so called, new Chinese Bundling Regulations for excipients and the findings of a recent survey. While the results of that poll will be published later, it is clear that it is early days for this new process and there are many questions as to the level of data which should be included in applications. The survey will be run periodically to build a picture of how implementation is going and it is hoped that this information will be useful in future discussions within IPEC and even with Chinese regulators themselves. As reported in a recent edition of Excipients Insights, the review of iron oxide E172, as a food additive being carried out by the Europe Food Safety Agency (EFSA. An industry-based consortium has been formed which will coordinate the generation of the requested safety data and as this may take two or more years, this is one subject which QRAC will monitor to determine if any actions might be required of IPEC Europe. The outputs of the recently formed working group on primary packaging materials for excipients were presented which should see the delivery of a position paper on how to address the various requirements for such components relative to the various regulations for chemicals, foods and pharmaceuticals, early in 2018. It’s always good to be able to inform members when an activity is completed and on this occasion, it was great to hear that the work to revise the IPEC Quality Agreement Guide is in its final stages. This now only needs approval at the IPEC Federation level, and it is anticipated that an official launch will take place in Q4 2017, accompanied by a webinar. Thanks to all contributors for their very hard work, and notably to Astrid Stockrahm for showing great determination to conclude this effort.

The other subjects discussed are listed in the agenda on the member’s site and the minutes of this and other QRAC meetings can be found there, too. But if you have any questions on any matter or want to suggest other areas of focus for QRAC, its chair, Johanna Eisele (pictured), is waiting to hear from you!



Book your place at the 2018 IPEC Europe Annual Excipients Forum

IPEC Europe is delighted to announce its 2018 Annual Excipients Forum will take place on 1 February at the Grand Hotel of Bordeaux.

Once again, this event will give delegates the opportunity to learn more about hot topics such as Chinese regulatory latest development, co-processed excipients, Quality by Design. the impact of excipients on process variability and so much more. You can take a look at the provisional programme, and don't wait to book your place now by clicking here.

For IPEC Europe members, Committee meetings will take place in the afternoon of Wednesday 31 January, and specific information will be sent by e-mail in due course. As usual, the Annual General Meeting (AGM) of IPEC Europe will take place on the day after the Annual Forum on 2 February. During the AGM, the Board of the association will review the past year, identify and further discuss with members the challenges and objectives for 2018.

Sponsorship opportunities

Interested in helping IPEC Europe to organise once again a high-level event? Have a look at the sponsorship packages and do not hesitate to contact the IPEC Europe Secretariat to discuss details and arrangements.

We look forward to meeting you in Bordeaux!



Introducing EXCiPACT webinar

IPEC Europe would like to invite you to the next EXCiPACT webinar on the EXCiPACT Excipient GMP Certification Scheme.

This webinar will take place on 11 October and focus on how to use supplier GMP certification to reduce the qualification and audit burden. The key learning objectives are:

  • the importance of appropriate GMP for excipients;
  • the critical factors that determine the suitability of independent certification schemes; and
  • the benefits of independent certification to both manufacturers and users of excipients.

For more information, please click here.



ICH Quality Guidelines: An Implementation Guide

Andy Teasdale, a principal scientist at AstraZeneca and team leader of IPEC Europe’s task force on ICH Q3D elemental impurities, has co-authored a new book entitled ICH Quality Guidelines: An Implementation Guide, which has been published by Wiley.

Examining the implications and practical implementation of multi-disciplinary ICH topics, the book – which covers topics such as stability testing, analytical method validation, impurities, biotechnology drugs and products, and good manufacturing practice (GMP) – gives an integrated view of how the guidelines inform drug development strategic planning and decision-making.

“ICH guidelines have undoubtedly made a positive contribution to the management of many key quality and safety aspects associated with production of safe and efficacious pharmaceuticals.  They have helped establish a harmonised framework in terms of requirements, one applied across ICH regions and beyond,” commented Teasdale.

“However, guidelines can only go so far leaving the challenge in many cases around how to practically apply the guideline concerned. This book is focused specifically on that practical implementation challenge.” 

It aims to provide that additional guidance, where possible through example, to assist in the pragmatic implementation of these guidelines, according to Teasdale, who notes that while each guideline is considered as individually through a dedicated chapter, throughout the book the interrelationship between guidelines is evaluated.

The intention is to provide – for the first time – an overall holistic framework of practical guidance in this important area, he said.

The book is co-authored by David Elder, a director within GlaxoSmithKline’s platform technology and science (PTS) function, and Raymond Nims, a senior consultant at RMC Pharmaceutical Solutions.



IPEC Europe calendar

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



PDG meets with IPEC Federation in Rockville

The annual meeting between the IPEC Federation and Pharmacopoeial Discussion Group (PDG) took place on 13 September in Rockville, Maryland, providing an opportunity to review of the PDG’s deliberations from its previous two-day meeting, which takes place ahead of the IPEC discussions, and the development of a ‘to do’ list of projects for the two parties.

IPEC Federation chair Patricia Rafidison (pictured) gave Excipients Insight an update on the deliberations, including a plan to restructure the PDG meeting format to facilitate technical exchange so the face-to-face meeting can focus on strategy.

This includes streamlining the process for the harmonization work programme with the purpose of improving efficiency and developing multiple ways to achieve harmonisation (bilateral, or others), plus other structured ways, e.g. bilateral or other mechanisms under Good Pharmacopoeial Practices. PDG will monitor these activities. 

Both parties’ current projects and plans were discussed, said Rafidison. On the agenda were cellulosics viscosity, pregelatinized starch identification studies, and silicon dioxide on round-robin testing. Elemental impurities harmonised testing methodology and proposals for specific elemental impurities were also covered. Input from the industry on the list of monographs that will retain elemental impurities in their monographs is expected.

There was also discussion on future harmonisation efforts, including integration of other pharmacopoeias such as China and India. PDG says it does not intend to expand but rather to use alternative ways to achieve harmonization with other bodies.



Third-party certification - Japanese style

Third-party certification of excipients GMP and GDP is fast gaining traction in the industry thanks to the activities of EXCiPACT and other organizations, but it is worth noting that other schemes operate in other parts of the world.

 The GMP Auditing Board for Pharmaceutical Excipients (GAB) is a voluntary certification scheme established by IPEC Japan in 2005 to help ensure that excipients meet high quality standards and meet the requirements of pharmaceutical product developers.

In this system, pharmaceutical companies can request the GAB to perform audits from the point of view of the finished product manufacturer as a customer.

The GAB was set up to provide independent, third-party certification – through the use of site audits – that excipients meet appropriate GMP standards. It uses standards originally developed by IPEC Japan’s GMP Committee in the 1990s and which have latterly been revised to bring them into conformity with the Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients.

The results of these audits are also shared via a scheme known as PEGASS (Pharmaceutical Excipients GMP Audit Sharing System), in which members collectively contract an audit and the audit outcome is shared among them. This allows excipient manufacturers to request GAB to carry out a standardised audit that can then be shared among multiple potential customers.

With thanks to Hiroshi Watanabe of Hinetsu’s Cellulose & Pharmaceutical Excipients Department, who kindly provided English language information on the GAB and PEGASS schemes.



IPEC Federation looks back on successful visit to China

The IPEC Federation spent a productive week in China over the summer, not only holding their latest board meeting in Beijing in mid-July but also taking the opportunity to participate in external events, including an educational workshop with the China’s Center for Drug evaluation and ExcipientFest Asia, for which the association was a co-sponsor.

The CDE workshop provided an opportunity for discussion on topics such as risk assessment and its role in the registration of excipients, the use of drug master files, regulatory inspection practices and supplier management programmes, amongst many other topics.Federation provided highlights insights on excipients regulation in US and Europe which included regulators’ expectations.

Meanwhile, IPEC was well represented in the ExcipientFest Asia programme: in addition to describing comprehensive overviews of the regulatory framework for excipients in Europe and the USA (with presentations from Patricia Rafidison, Dave Schoneker, and Priscilla Zawislak), the implementation of ICHQ3D in those regions and safety considerations for different types of excipients were presented by Janeen Skutnik-Wilkinson and Dave Schoneker, respectively, and Adrian Bne covered the topic of excipient auditing best practices.

It was an opportune time for the Federation to elevate its attention on China, particularly in light of ongoing regulatory developments at the China Food and Drug Administration (CFDA) and Chinese Pharmacopoeia (ChP), according to the association’s chair Patricia Rafidison.

“CFDA has joined ICH, and has an accelerated programme to revise regulations governing medicinal products and medical devices. It will be interesting to see how this impacts harmonization,” said Rafidison. “Of course, our hope is that efforts are taken to ensure China’s standards are in alignment with other ICH regions.”

She extended heartfelt thanks to IPEC China, saying the association’s close involvement “has been critical to be able to keep track of regulatory development in China and to facilitate a dialogue with users and suppliers of excipients there as well as the authorities.”



EMA adds new excipients to labeling requirements

As this edition went to press, the European Medicines Agency (EMA) and the European Commission updated the annex to the Commission guideline on excipients in the labelling and package leaflet of medicinal products for human use.

The updated annex, which contains all excipients that must be declared in a medicine’s labelling and package leaflet and their agreed safety warnings, includes five new excipients as well as new safety warnings for ten existing excipients.

"The main aim of this update is to take into account safety concerns which are not currently addressed in the existing annex to the guideline," said the EMA in a statement. "It also pays specific attention to, for example, the safety of these excipients when used in children or pregnant women."

The updated annex takes account of the comments received for each excipient during public consultations, it continues. The additions and updates apply to: aspartame; benzalkonium chloride; benzoic acid (E120 and benzoates); benzyl alcohol;  boric acid (and borates); cyclodextrins; fragrances containng allergens; fructose; phenylalanine; phosphate buffers; propylene glycol (E1520) and esters of propylene glycol; sodium; Sodium laurilsulfate (E487); sorbitol (E420); and wheat starch (containing gluten).



PQRI/USP schedule elemental impurities workshop

On November 2-3, the Product Quality Research Institute (PQRI) and US Pharmacopeia (USP) will hold a joint workshop on ICH Q3D Elemental Impurities at the USP meeting centre in Rockville, Maryland.

The implementation of the ICH Q3D guideline will go into full effect in the US and Europe in 2018 for all products. The Q3D guideline has been applied to new drug applications in the US and Europe since June 1, 2016.  This workshop will provide an overview of the first 16 months of compliance experience and will review ongoing work throughout industry to resolve challenges involved in global implementation of the elemental impurities (EI) guidelines and standards.

Specific topics will include the following:

  • Update on Recent US/EU/JP Regulatory Guidance, Compendial Chapters and further ICH EI Initiatives
  • Company and regulator experience with implementation for new drug applications since June 2016
  • Implementation of Q3D requirements for OTC and existing Prescription Drugs in January 2018 – Challenges and Expectations
  • Acceptable Risk Assessment Strategies
  • Global Developments for EI Requirements
  • PQRI Phase 2 Collaborative study - outcomes and recommendations
  • Outstanding Analytical Challenges

The workshop will include global experts from ICH Q3D IWG, industry, regulatory authorities, pharmacopeias, and academia who are intimately involved in this area. More information is available here.



With staff retention an issue, EMA reveals favoured host cities

The European Medicines Agency (EMA) says it could lose the bulk of its staff if the move from its current home in the UK isn’t handled well, and it has been reported that Amsterdam, Barcelona, Copenhagen, Milan and Vienna are the favoured locations.

Ahead of an assessment of the bids by 19 cities who are in the running to locate the agency later this month, the EMA surveyed its staff to see how they are feeling about the prospects of a move, and the results make alarming reading.

For certain locations staff retention rates could be significantly less than 30%, it says, which would render the EMA unable to function and would have “important consequences for public health in the EU.”

Even the best-case scenario emerging from the survey puts the EU regulator as losing 19% of its workforce, and two-thirds of workers are adamant that the new EMA location will be a determining factor in their decision-making to relocate or not.

The results “emphasize the importance of the upcoming decision on the EMA’s future seat as the retention of skilled and experienced staff is crucial for the agency’s continuity of operations,” said the EMA in a statement.

The time the EMA thinks it could take to regain full operational capacity is also alarming.  Assuming one of the five [preferred cities are selected – which could see on average around of quarter of staff being lost – it will take two to three years to get back up to speed.

The middle range sees recovery in the three to 10-year time frame, while the bottom eight city locations would result in “permanent damage to the system” and a need for emergency legislative measures at EU and national level to keep the regulatory regime operational.

If a favoured location is chosen the disruption would amount to some delays in approving new medicines, and slower progress on public health initiatives. At the other extreme, says the EMA, is a “public health crisis” and an “unravelling of the single market for medicines [with] no centralised authorisations.” That would lead to patient deaths and the likelihood of litigation, it asserts.

The applications are being assessed on the basis of six criteria, with the European Commission’s decision – which has already been delayed - due in November. Some observers see the timing of the survey as an attempt to pre-empt any politically-motivated decision to shift the EMA to one of the newer EU nations that do not host any of the EU’s agencies.

The full list of cities and countries offered to host the EMA

Amsterdam (The Netherlands)

Athens (Greece)

Barcelona (Spain)

Bonn (Germany)

Bratislava (Slovakia)

Brussels (Belgium)

Bucharest (Romania)

Copenhagen (Denmark)

Dublin (Ireland)

Helsinki (Finland)

Lille (France)

Milan (Italy)

Porto (Portugal)

Sofia (Bulgaria)

Stockholm (Sweden)

Malta (Malta)

Vienna (Austria)

Warsaw (Poland)

Zagreb (Croatia)



New EU GMP Directive separates finished and investigational medicines

The European Commission has published a new Directive on the principles and guidelines of good manufacturing practice for human-use medicinal products, which updates Directive 2003/94 and is due to come into effect on 31 March 2018.

Directive 2017/1572 was published on 15 September in the Official Journal of the European Union, with a delegated regulation Directive 2017/1569 published on the following day which sets out GMP guidelines for investigational medicinal products (IMPs).

Previously, IMPs were covered under 2003/94 along with licensed products and the intention is to separate these out into different documents for clarity and flexibility.

The EC carried out a public consultation two years ago to get feedback on the plans separate GMP for marketed and investigational drugs, saying that because GMP for IMPs “already exists and is generally well-functioning, there is no need to reinvent the wheel.”

Aside from solving the issue of deleting references to IMPs, Directive 2017/1572 also includes some updates to the definition of a pharmaceutical quality system and some terminology amendments “to reflect the international developments or the actual usage of that terminology of inspectors and manufacturers.”

A commentary on the changes by pharmaceutical GMP and quality management trainer Dominic Parry of Inspired Pharma Training notes that the 2017/1572 has an almost identical structure to the directive it replaces and maintains many of the same requirements.

There are a few changes, including updates to Article 3 - Inspection aimed at manufacturers of Advanced Therapy Medicinal Products (ATMPs) such as cell or gene therapies, which also now refers to a requirement for regulators to also operate within a formal quality system.

Meanwhile, the European Compliance Academy (ECA) notes that 2017/1569 also regulates the responsibilities of qualified persons (QPs) in the context of EU regulations on Good Clinical Practice (GCP), and describes the different requirements for IMPs manufactured within and outside EU member states.

Directive 2017/1572 has to be converted into national law, and member states are asked to adopt and publish the new legislation by March 31, 2018



EMA publishes paper on developing medicines for older population

The European Medicines Agency (EMA) has published a draft reflection paper on the development of medicines for use in older people, which includes a section covering excipients.

The paper “describes aspects that medicines developers may consider when designing medicines for older people, such as selecting appropriate routes of administration and dosage forms, dosing frequency, excipients, container closure systems, devices and technologies, and user instructions in the product information,” says the agency.

The section on excipients reads as follows:

Generally, the suitability of excipients in the older population needs to be considered in relation to:

  • the risk for altered safety profiles in case of impaired human organ and body functions;
  • conditions associated with ageing (e.g. coconut oil may increase cholesterol levels; sugars may increase blood glucose levels and may cause dental caries and further reduce oral health);
  • the likelihood of, and risk associated with, any excipient overload due to multiple medication use (e.g. sorbitol or mannitol overload may result in altered gastric transit times, laxative effect). 

Besides safety considerations, the potential benefits of excipients in preparations for older people also need to be considered, (e.g. colours may improve medication recognition and reduce the risk of unintentional swapping, preservatives may avoid the need for storage in the refrigerator).  

The reflection paper is open for public consultation until 31 January, 2018.



Brief: Turkey updates GMP guidance

The Turkish Medicines and Medical Devices Agency (TITCK) has updated its GMP Guide for Manufacturing Plants of Medicinal Products for Human Use, in order to bring it into alignment with recent updates to the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Specifically, the guide has been revised to take into account Part 1 – Chapters 1, 2, 6 and 7 of the latest edition of PIC/S GMP Guide (PE 009-13).,The latter was revised to align with the current EU GMP code and ICH Q10 and came into effect in January.

An English version of the new Turkish GMP guide is available here.



Recommended reading

A multifunctional mineral excipient

Orally disintegrating tablets (ODTs) are becoming increasingly important in the global pharmaceutical market for both prescription and over-the-counter medications because they can significantly improve patient compliance. They can be swallowed without the need for water, are generally smaller, and have good mouthfeel. Such properties make ODTs particularly convenient for children and the elderly, especially when a flavor is also incorporated into the formulation. In addition, they are the delivery format of choice for people who want to take their medicine “on the go” and are particularly helpful for patients who have difficulty swallowing--a complication associated with a number of age-related conditions, including stroke and Parkinson’s disease.


Using Quality by Design in the formulation of tablets and capsules

This article discusses the types of supporting activities and scale of operations that will help you get a new product filing accepted and eventually approved by the regulatory authorities.

Tablets & Capsules (Registration required)

Applying QbD in process development

Over the past few years, global regulatory authorities have been raising the expectation of incorporating quality by design (QbD) into pharmaceutical development. While QbD offers many important long-term benefits, these expectations are having a dramatic impact on product development groups and their supporting corporate informatics infrastructure. This article discusses how QbD requirements for risk assessment, process assessment, material assessment, documentation, and traceability can be addressed with informatics, using development of an impurity control strategy as an example.


Eye on Excipients: Taste modulation

This edition of the column discusses the genesis and development of ClearTaste, a novel taste-modulating excipient based on the use of solid-state myceliation.

Tablets & Capsules (Registration required)



Download IPEC 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
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  • 2014 The IPEC Significant Change Guide: Third revision
    Download PDF
  • 2013 The IPEC Certificate of Analysis Guide
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  • 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.

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

PQRI/USP Workshop on ICH Q3D Elemental Impurities Requirements
Rockville, Maryland, US - 2-3 November 2017
More information here.

Definition of Starting Materials - Scientific and Regulatory Aspects
Frankfurt/Main, Germany - 8 November 2017
More information here.

2017 ISPE UK Annual Conference
Stratford-upon-Avon, UK - 30 November, 2017
More information here.

2018 IPEC Europe Annual Excipients Forum
Bordeaux, France - 1 February 2018
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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