Expanding Excipient Portfolios - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Expanding Excipient Portfolios
Excipient manufacturers expand production capacity and partner to broaden their offerings.

Pharmaceutical Technology
Volume 36, Issue 4, pp. 72-75

Regulatory developments

Excipients also are an important area for regulation and related standards. Several recent developments include the launch of EXCiPACT, a draft FDA guidance to limit use of certain phthalate-based excipients, and proposed revisions to European excipients guidelines on labeling with respect to pediatric provisions.

EXCiPACT . In late January 2012, EXCiPACT, a new, voluntary international certification scheme, was launched. It was designed and developed to ensure that cGMP and current good distribution practices (cGDP) standards are being used in the manufacture and supply of pharmaceutical excipients. The scheme is a product of a mulitstakeholder effort, which included participation from the European Fine Chemicals Group (EFCG), the International Pharmaceuticals Excipients Council (IPEC) of the Americas, IPEC–Europe, the European Association of Chemicals Distributors, and the Pharmaceutical Quality Group.

The EXCiPACT scheme provides independent certification of manufacturers and suppliers of pharmaceutical excipients as a means of ensuring patient safety through supplier quality while minimizing overall supply-chain costs. The EXCiPACT standards act as annexes to ISO standards 9001, 19011, and 17021. Suppliers who do not hold ISO 9001 certification will be able to obtain an equivalent certificate through the forthcoming US national standard (ANSI–NSF 363), which also uses the EXCiPACT cGMP and cGDP standards, according to an EFCG analysis.

Phthalates-based excipients. In March 2012, FDA issued a draft guidance Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products to provide the Center for Drug Evaluation and Research's thinking on the potential human health risks associated with exposure to dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) (1). In particular, the draft guidance recommends that the pharmaceutical industry avoid the use of these two specific phthalates as excipients in CDER-regulated drug and biologic products, including prescription and nonprescription products. The draft guidance does not address the use of DBP or DEHP in other types of FDA-regulated products or exposure to DBP or DEHP due to the presence of any of these compounds as an impurity, including as a result of leaching from packaging materials. The comment period for the draft guidance ends May 31, 2012.

Phthalates are found in certain pharmaceutical formulations, primarily as a plasticizer in enteric coatings of solid oral drug products to maintain flexibility (1). According to FDA's draft guidance, DBP and DEHP have been shown to be developmental and reproductive toxicants in laboratory animals. While the data in humans are less clear, epidemiological studies suggest that certain phthalates may affect reproductive and developmental outcomes. Although the human data are limited, FDA has determined that there is evidence that exposure to DBP and DEHP from pharmaceuticals presents a potential risk of developmental and reproductive toxicity and suggests that safer excipient alternatives to DBP and DEHP are available and should be used (1).

Pediatric considerations for excipients. In March 2012, EMA issued a concept paper to gain public input regarding revisions to its excipient guidelines on labeling and packaging to include safety concerns for pediatric populations and pregnant women (2). The current excipient guideline was last revised in July 2003 and does not address safety concerns regarding excipients as they relate to pediatric populations as had been addressed in other European regulations covering pediatric populations for pharmaceuticals (3, 4).

"It is important to note that the safety of excipients can affect children differently than adults due to the ongoing organ development and incomplete maturation depending on the age," stated EMA in its concept paper (2). EMA also noted in its concept paper that pregnant women are not covered in the excipient guidelines and that "safety labeling is needed for products intended for use in this population to ensure the safety of the unborn child(ren)" (2).

The public comment period ends at the end of May 2012. EMA also said in its concept paper that the labeling of several excipients are specified for a limited number of routes of administration and additional routes of administration need to be added. Also, the guidelines need to be expanded to include additional excipients (2). The draft revised guideline is expected to be released for a six-month month external consultation in the third quarter of 2013 to the first quarter of 2014. After the external consultation, the final guideline is expected to be available within 6–12 months.

Patricia Van Arnum is a executive editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072,


1. FDA, Draft Guidance for Industry: Limiting the Use of Certain Phthalates as Excipients in Center for Drug Evaluation and Research-Regulated Products; Availability Fed. Reg. 77 (42), 12852 (2012).

2. EMA, Concept Paper on the Need for Revision of the Guideline on Excipients in the Label and Package Leaflet of Medicinal Products for Human Use (CPMP/463/00) (Feb. 6, 2012).

3. EC, Guidelines: Medicinal Products for Human Use: Safety, Environment and Information: Excipients in the Label and Package Leaflet of Medicinal Products for Human Use (Brussels, July 2003).

4. EC Regulation No. 1901/2006, Pediatric Regulation (Brussels, Dec. 2006).


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Source: Pharmaceutical Technology,
Click here