What Are the Latest Guidelines for Excipients?

Pharmaceutical Outsourcing, July, 2016

The global outlook for excipients looks bright, as the market is expected to grow at an annual compound rate of of 7.6% from 2015 to 2020, reaching $6.4 billion by 20201. The major factors driving market growth are the growing demand for pharmaceutical products and functional excipients, the increasing generic drug market, and the emergence of new excipients. Drug manufacturers also rely on excipients to develop value-added and distinct products at a lower cost without compromising quality, such as extended-release formulations.

The industry seeks novel multifunctional excipients that can improve solubility and absorption, enhance disintegration and increase stability for biologics/parenteral formulations. Novel excipients are also in high demand for developing novel drug delivery systems, such as nanotechnology-enabled and liposomal delivery systems. Co-processed excipients, combining two or more existing excipients into one product, are expected to gain market approval faster than those with a completely new chemical entity.

According to the 2015 Nice Insight Excipient Survey2 of 412 drug manufacturers who acquire excipients and 189 excipients suppliers, 28% of buyers spend $1 million to $10 million annually for excipients and more than one third spend $10 million to $100 million. The majority of excipients buyers were from emerging, niche and startup companies (24%), as well as biotech/biologics (23%) and big pharma companies (23%).

However, despite the positive outlook, a number of looming issues can weaken the growth of this market, including increasingly stringent regulatory requirements, supply chain issues, declining investments in R&D by pharmaceutical excipient producers and high market fragmentation. In this article, we look at the impact of current regulatory expectations, supply chain issues and other industry challenges.

Regulatory Guidelines and Requirements

Excipients are present in the final drug product, but contaminated products must not reach patients.

Detailed below are some of the latest global guidelines for excipient risk assessment and ensuring product safety:

EMA Guidelines on Excipient Risk Assessment (2015)

Last year, the European Union issued, "Guidelines of 19 March 2015 on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use." Pharmaceutical manufacturers were challenged to implement the guidelines for products in development or authorized by March 21, 2016, including performing a risk assessment of each of its excipient suppliers to determine the GMP expectations. This risk assessment can be obtained through audit or from information received from the excipient manufacturer.

The guidelines' requirements for determining and ensuring appropriate GMP are challenging and result in a significant initial expense. Companies must extend their risk profiles for excipients to comply with the new requirements. The appropriate GMP and risk profiles for both the excipient and the excipient manufacturer have been prepared for all authorized products in less than a year. While most industry companies and organizations agreed on the need for such guidelines, the major concern was meeting the short deadline, as well as the costs, for compliance.

IPEC and Supply Chain Security

The International Pharmaceutical Excipient Council (IPEC) is an industry group that focuses on harmonizing compendia, and produces GMP and GDP standards for pharmaceutical excipients internationally. Its publications  IPEC-PQG (Pharmaceutical Quality Group) GMP Guide 2006 and IPEC GDP Guide 2006  are broadly recognized as industry standards and are voluntarily applied to excipient manufacturing and distribution.

In May 2015, IPEC responded to the EMA guidelines by issuing a position paper supporting risk assessment, but with concerns over timing. The paper also emphasized that collaboration, communication and cooperation along the entire supply chain is necessary to avoid gaps in a holistic risk-assessment process. Further, IPEC views third-party auditing and certification programs and national standards, such as NSF/IPEC/ANSI 363-2014 and EXCiPACT GMP and GDP standards, as essential to comply with the new requirements to qualify excipients and their suppliers.

The IPEC guidance helps ensure minimal contamination and consistent product. The authorities in Europe, and to a growing extent in the US, are looking for drug product manufacturers to be in control of their entire supply chain. This is to better understand what their excipient manufacturers are doing, how they control their processes and the potential contaminants and impurities.

Given the cost of auditing suppliers, regulators in the U.S. and Europe have encouraged manufacturers to work with third-party auditors to certify that they are using raw materials that meet current good manufacturing practices (cGMP). A number of programs are available to conduct auditing of an excipient manufacturer, including IPEC's joint audit service and the U.S. Pharmacopeial Convention's (USP's) excipient verification program and certification scheme. The EXiPACT certification scheme provides independent auditing and certification of excipient manufacturers, suppliers and distributors, to ensure they are in line with cGMP and current good distribution practices (cGDP) throughout the pharmaceutical supply chain. These auditing services are available to help minimize costs and time for both excipient suppliers and drug product manufacturers.

IPEC's position paper emphasizes that the assessment of all associated risks of an excipient and its suppliers can only be achieved by the manufacturing authorization holder through open communication, collaboration and flow of information between all parties along the excipient supply chain. This collaboration is critical to avoid gaps in a holistic risk-assessment process. For example, the risk-assessment application process could lead to situations in which an excipient from a single manufacturer could be classified by different manufacturers into different risk classes (low, medium, high), depending on its intended use and application. This could result in differing expectations relating to the appropriate GMPs necessary in the manufacture of the same excipient.3

ANSI Standard Released in the U.S.

In the U.S., the first American National Standard for GMP of pharmaceutical excipients, NSF/ IPEC/ANSI 363, was published in 2015 by NSF International: Good Manufacturing Practices (GMP) for Pharmaceutical Excipients. The new standard and auditing program assists pharmaceutical companies in verifying regulatory compliance and strengthening safety and quality throughout the excipient supply chain. The standard incorporates a risk assessment process that can be applied to any excipient and a framework for excipient quality control that is consistent with the ICH Q 8-10 principles.

The NSF/IPEC/ANSI 363 standard for pharmaceutical excipient GMPs provides a harmonized and comprehensive set of criteria for the quality management systems used in the manufacture of pharmaceutical excipients worldwide. Also, the Food and Drug Administration Safety and Innovation Act (FDASIA) now requires U.S. manufacturers to verify and document that the raw materials used in finished products are also meeting appropriate GMPs. Drug makers are expected to conduct audits of excipient manufacturers and distributors to ensure a secure supply chain.

Supply Chain Issues

The IPEC-PQG GMP Guide 2006 and IPEC GDP Guide 2006 provide the basis for managing a quality-based, safe, and traceable pharmaceutical excipients supply chain. According to these guidelines, all parties in the supply chain must share responsibility for the quality and safety of the materials and products. Ultimately, the drug manufacturer is accountable for assessing the risk in the supply chain, implementing a risk management program, and having a risk mitigation strategy in place. The manufacturer must have complete knowledge of the supply chain, the history and reputation of each party involved, practices followed at each step, and match risk and controls with audit and verification throughout the supply chain.

There are multiple complex issues in the global excipient supply chain, particularly when excipients are imported. Concerns about imports have been raised as the excipient industry has experienced more FDA import holds. An unexpected hold can delay drug production, negatively impacting its timeline to market or cause a shortage in drug supply, which can have devastating consequences. Other supply chain challenges include a supplier not agreeing to an audit or many global locations to audit. In-house auditors maybe unfamiliar with chemical processing; there is also a concern surrounding travel costs and language barriers. As a result, third-party auditing services are practical and save costs.


  1. World Excipients Market Expected to Reach $6.4 Billion by 2020, Allied Market Research. Drug Development & Delivery. April 2016. Accessible at:  http://drug-dev.com/Main/Back-Issues/World-Excipients-Market-Expected-toReach-64-Billi-1101.aspx
  2. Nice Insight 2015 Excipients Study
  3. Van Arnum P, Quality Risk Assessment for Excipients: An Industry Perspective. DCAT Value Chain Insights, May 26, 2015.


Guy Tiene

Guy supports the success of life science organizations by identifying synergies across research, content, marketing and communications resources to drive value for clients. With over 30 years of education and marketing experience and 18 years in the life sciences alone, Guy leads our editorial standards for client content, Pharma’s Almanac and Nice Insight research-based industry content as well as external communications for clients. Having served as head of global marketing and communications for a CMO, he also brings critical insight and guidance to all communications. Guy holds a Masters degree from Columbia University.