Excipients presentation-part 1-definition and regulation

1
Pharmaceutical Excipients – Part 1
March 2018
Philippe Tschopp – Founder www.pharmaexcipients.com

2www.pharmaexcipients.com
Part 1 Outline
a) Definitions
b) Regulations
c) Excipient Market

What are pharmaceutical Excipients?

“The word excipient is derived from the Latin excipere, meaning 'to except', which
is simply explained as 'other than'. Pharmaceutical excipients are basically
everything other than the active pharmaceutical ingredient. Ideally, excipients
should be inert, however, recent reports of adverse reactions have suggested
otherwise.” (Australian Prescriber)
“Pharmaceutical excipients are substances other than the active
pharmaceutical ingredient (API) that have been appropriately evaluated for
safety and are intentionally included in a drug delivery system.”
Pharmaceutical Excipient Definition

How many pharmaceutics do you know
which think that pharmaceutical drugs only
consist of API?
What is the average amount of excipients in a
solid dosage formulation?
How many different excipients do you find in
solid dosage formulation?
Excipients – what for?

What is the role of a pharmaceutical Excipient?

Main Roles of Pharmaceutical Excipients
Check Basics Chapter in : www.pharmaexcipients.com

What are the Ideal Pharma Excipient Properties?

Ideal properties of a Pharmaceutical Excipient
Check Basics Chapter in : www.pharmaexcipients.com

Where do you find information on pharmaceutical excipients how to
identify, test, release, etc.?
Pharmaceutical Excipients

Pharma Excipients are defined in the major pharmacopoeias:
• The European Pharmacopoeia (Ph. Eur.)
• United States Pharmacopeia– National Formulary (USP–NF)
• Japanese Pharmacopoeia (JP)
as well as in national pharmacopoeias. The industry standards are based
on the 3 major ones listed above.
Major Guidelines by FDA, EMA and other Health Authorities
Pharmaceutical Excipient Definition

NF contains excipients standards with references to allied reference materials.
*First published in 1888 by the American Pharmaceutical Association
**Shangraw, Ralph Ph.D., Drug Development and Industrial Pharmacy, 13(13), 2421-2439 (1987),
Compendial Standards for Excipients
History of the National Fomulary
History of National Formulary
U.S.P. (1820)
Drugs and
Excipients
The National
Formulary of
Unofficial
Preparations *
(1888) Drugs and
Excipients
U.S.P./N.F (1980)
(USP Drugs) (NF
Excipients**)

1888 National Fomulary Monograph

The first edition of the National Formulary (NF) originally named “The National
Formulary of Unofficial Preparations” was first published in 1888 by the
American Pharmaceutical Association.
USP was founded in 1820. However, instead of working in competition with the
USP, the NF served as a complement to it.
While the USP served to set standards for base drugs, the NF served to
standardize the higher-level or compound drugs which made use of more than
just one base drug. These included formulations and unofficial preparations for
widely sold products.
Background on the National Fomulary

USP today‘s activities

• Developing new monographs
• Pending monographs- http://www.usp.org/usp-nf/pending-
monographs
• Updating/modernizing existing monographs
• Harmonization of Excipient Monographs
• Reformatting (‘monograph redesign’)
USP today‘s activities

18 – 24 months
USP-NF Monograph Development

Harmonization of Excipient Monographs

Example: Carboxymethylcellulose Calcium
The PDG harmonized
standard for
Carboxymethylcellulose
Calcium reduced 37 non-
harmonized tests to 10
tests (Table 1), which
greatly helps industry
save resources and
improve efficiency.
Challenges and Opportunities in Developing
Up-to-Date USP–NF Excipient Monographs –
American Pharmaceutical Review, Jan 2016

Example: Tributylacetylcitrat
„Pharmazeutische Hilfsstoffe“ Peter C. Schmidt · Siegfried Lang

• International regulatory standards
• Cost reduction
• Reduced falsification possibilities
• Etc.
Importance of Harmonisation

Acquisitions & Merger Highlights of the last years
Company Action Company
Dupont Acquired Dow
Lonza Acquired Capsugel
Roquette Acquired Blanver
Colorcon Acquired NP Pharm
Rhodia Acquired Albright & Wilson
Innophos Acquired Rhodia
J. Rettenmaier Acquired Penwest Excipients
WR Grace Acquired Synthetech
Dow Acquired Wolff Cellulosics
J. Rettenmaier Aqcuired Demacsa
DMV/Fonterra Merges DFE formed

Excipient Market & Regulations
Value of Excipient in a pharmaceutical product?
500 mg Paracetamol
Maize starch, potassium sorbate,
purified talc, stearic acid, polyvidone,
starch pregelatinised, hypromellose
and triacetin.

API cost are approx 2-5% of the final price in a Pharmacy (AVP)
Manufacturing cost are approx. 9-14% of the final price (AVP)

The global pharmaceutical excipients market, a multibillion market, is
projected to expand at a healthy pace of 6.7 percent annually in the next
five years and reach $8.4 billion by 2019 (Markets and Markets, 2015).
This continued growth is largely driven by the increasing demand for
pharmaceutical products to serve an aging population and improve
healthcare worldwide. Despite the positive outlook, the industry itself
faces a variety of challenges to meet the expectations of the regulators,
end users/drug makers and ultimately the patients.
“Challenges Facing Pharmaceutical Excipients” March 2015 American Pharmaceutical Review

“Challenges Facing Pharmaceutical Excipients” March 2015 American Pharmaceutical Review

What are the most used excipients?
Magnesium Stearate
Microcrystalline Cellulose
Starch (corn)
Silicone Dioxide
Stearic Acid
Sodium Starch Glycolate
Talc
Sucrose
HPMC
OPA products
Croscarmellose
Hydroxypropyl Cellulose
Ethycellulose
Calcium Phosphate
Crospovidone
Shellac
Calcium Stearate
Glycerin
Lactose
Titanum Dioxide
Carboxymethylstarch
Gelatin
Acaia

“Major Excipients in US medicinal products as per “Pharmaceutical Excipients – The Past and Future - Ermens 2004-”

Apart from regulatory legislations, the pharmaceutical excipient industry
has long been taking their own steps to ensure the safety and quality of
excipients. Back in 1991, the industry formed the International
Pharmaceutical Excipients Council (IPEC), an industry group focusing
on harmonizing compendia, GMP and GDP standards for
pharmaceutical excipients internationally. Its publication of IPEC-PQG
(The Pharmaceutical Quality Group) GMP Guide 2006 and IPEC GDP
Guide 2006 have been recognized as industry standards and applied in
excipient manufacturing and distribution voluntarily. A new revised IPEC-
PQG GMP and IPEC GDP Guide was published by the end of 2017.

European Perspective
• 2011 Falsified Medicines Directive 2011/62/EU
Qualification of excipient suppliers
• 2014 Revision of EU GMP Part 1 Chapter 5
Production – starting materials, 5.29 excipients
• 2015 Guidelines on the formalized risk assessment for ascertaining
appropriate good manufacturing practice for excipients of medicinal
products for human use - to have been implemented by 21st March
2016 – see also: “The IPEC Risk Assessment for Pharmaceutical
Excipients. Part I - Risk Assessment for Excipient Manufacturers”
“EXCiPACT Presentation Making Pharmaceuticals, Birmingham May 2016”

2011/62/EU Falsified Medicines Directive, article 46 (f) :
‘The holder of the manufacturing authorisation shall ensure that the
excipients are suitable for use in medicinal products by ascertaining what
the appropriate good manufacturing practice is. This shall be ascertained
on the basis of a formalised risk assessment...’
Eudralex Vol 4, Part 1, Chapter 5 Starting Materials, section 5.27:
‘The selection, qualification, approval and maintenance of
suppliers....should be documented as part of the pharmaceutical quality
system. The level of supervision should be proportionate to the
risks.....The supporting evidence for each supplier / material approval
should be maintained.’
“EXCiPACT Presentaton Making Pharmaceuticals, Birmingham May 2016”

European Commission Guideline EC2015/C95/02 on the formalized
risk assessment for ascertaining appropriate good manufacturing
practice for excipients of medicinal products for human use ……to have
been implemented by the Manufacturing Authorisation Holder (MAH)
by 21st March 2016
• To determine the GMP required the MAH (the user) has to evaluate
the risks posed
• by the excipient in terms of the nature of the substance and
• by the approved suppliers who provide that substance
• These suppliers can be the Manufacturer of the excipient or a
Distributor

US perspective: Excipients are Drugs
• Federal Food, Drug and Cosmetic Act Section 501(a)(2)(B)
Adulteration Provision
“A drug shall be deemed adulterated - if... the methods used in, or the facilities or controls used for, its manufacture, processing,
packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing
practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets
the quality and purity characteristics, which it purports or is represented to possess.”
• Subject to inspection under FDA (Section 704(a)(1) of the Act)
however, inspections will only be conducted by special assignment or
for cause
“EXCiPACT Presentation Making Pharmaceuticals, Birmingham May 2016”

• Major excipient manufacturer are large chemical producers of which
the pharmaceutical application of their products is only a small part of
the business
• Altough excipients should be inert and “non-active” they make most of
the formulation and have more functionalities as initially thought of
• Complex supply chains need clarification for more security
Why all these Regulations?

MCC SSG Calcium Carbonate
Why all these Regulations?

Outline – Next Presentation part will be on
1 Introduction, Definitions, Regulations & Excipient Market
2 Types and manufacturers of Excipients
If you have any question please contact us at:
info@pharmaexcipients.com

Excipients presentation-part 1-definition and regulation

More Related Content

What's hot

Similar to Excipients presentation-part 1-definition and regulation

Recently uploaded

Excipients presentation-part 1-definition and regulation