What’s New in the Second Edition:
Updated examples and additional rules of thumb
"How to" pages cover actions such as how to design a workstation
Coverage of RULA, Strain Index, and TAPDA
In short, the plan of the book is that Part I provides help on how to think and Part II help on how to measure. The non-quantitative materials come first, since creativity in the application of the principles and rules provides greater value.
Based on 35 years of practical problem-solving in over 1,500 workplaces, the book provides a down-to-earth and practical guide for solving ergonomics problems. It provides a framework for evaluating tasks using low-tech, non-quantitative methods, along with an overview of the standard measuring systems for those occasions when numbers are needed.
See What’s in the New Edition:
Four case studies Addition of another co-author Examples that reflect current technology Information on Critical Path Analysis (CPA)
The authors highlight where ergonomics methods fit in the design process and how to select a method appropriate for your purpose. They describe each method, supplying an overview, instructions on how to carry out an analysis, a mini bibliography, pros and cons, one or more examples, and a flow chart. They then rate each method for reliability/validity, resources, usability, and efficacy. The book then examines data from studies on training, reliability, and validity, and presents an equation that enables you to calculate approximately the financial benefits of using each method.
Based on research and expertise, the book gives you the freedom to be adventurous when choosing methods and the foundation to choose the method that fits the task at hand. Written by experts, it also helps you hone your skills and put the craft of ergonomics into practice.
As with the earlier editions, the main purpose of this handbook is to serve the needs of the human factors and ergonomics researchers, practitioners, and graduate students. Each chapter has a strong theory and scientific base, but is heavily focused on real world applications. As such, a significant number of case studies, examples, figures, and tables are included to aid in the understanding and application of the material covered.
evolving as new materials, methods, and machines become
readily available to produce more reliable, stable, and releasecontrolled
formulations. At the same time, globalization of
sourcing of raw and finished pharmaceuticals brings challenges
to regulatory authorities and results in more frequent
revisions to the current good manufacturing practices, regulatory
approval dossier requirements, and the growing need
for cost optimization. Since the publication of the first edition
of this book, a lot has changed in all of these areas of importance
to pharmaceutical manufacturers. The second edition
builds on the dynamic nature of the science and art of formulations
and provides an evermore useful handbook that
should be highly welcomed by the industry, the regulatory
authorities, as well as the teaching institutions.
The first edition of this book was a great success as it
brought under one umbrella the myriad of choices available
to formulators. The readers were very responsive and communicated
withmefrequently pointing out to the weaknesses
as well as the strengths of the book. The second edition totally
revised attempts to achieve these by making major changes
to the text, some of which include:
1. Complete, revised errors corrected and subject matter
reorganized for easy reference. Whereas this series has
six volumes differentiated on the basis of the type of
dosage form and a separate inclusion of the U.S. OTC
products, ideally the entire collection is needed to benefit
from the myriad of topics relating to formulations,
regulatory compliance, and dossier preparation.
2. Total number of pages is increased from 1684 to 2726.
3. Total number of formulations is expanded by about 30%
with many newly approved formulations.
4. Novel formulations are now provided for a variety of
drugs; these data are collected from the massive intellectual
property data and suggest toward the future trend
of formulations. While some of these formulations may
not have been approved in the United States or Europe,
these do provide additional choices, particularly for the
NDA preparation. As always, it is the responsibility of
the manufacturer to assure that the intellectual property
rights are not violated.
5. A significant change in this edition is the inclusion of
commercial products; while most of this information
is culled out from the open source such as the FOIA
(http://www.fda.gov/foi/default.htm), I have made attempts
to reconstruct the critical portions of it based
on what I call the generally acceptable standards. The
drug companies are advised to assure that any intellectual
property rights are not violated and this applies to
all information contained in this book. The freedom of
information act (FOIA) is an extremely useful conduit
for reliable information and manufacturers are strongly
urged to make use of this information. Whereas this information
is provided free of charge, the process of obtaining
the information may be cumbersome, in which
case, commercial sources of these databases can prove
useful, particularly for the non-U.S. companies.
6. Also included are the new Good Manufacturing Guidelines
(2007) with amendments (2008) for the United States
and similar updates for European Union and WHO; it is
strongly urged that the companies discontinue using all
old documents as there are significant changes in the revised
form, and many of them are likely to reduce the
cost of GMP compliance.
7. Details on design of clean rooms is a new entry that will
be of great use to sterile product manufacturers; whereas
the design and flow of personnel and material flow is of
critical nature, regulatory agencies view these differently
and the manufacturer is advised always to comply with
most stringent requirements.
8. Addition of a self-auditing template in each volume of
the series. While the cGMP compliance is a complex issue
and the requirements diversified across the globe, the
basic compliance remains universal. I have chosen the
European Union guidelines (as these are more in tune
with the ICH) to prepare a self-audit module that I recommend
that every manufacturer adopt as a routine to
assure GMP compliance. In most instances reading the
template by those responsible for compliance with keep
them sensitive to the needs of GMP.
9. OTC products cross-referenced in other volumes where
appropriate. This was necessary since the regulatory authorities
worldwide define this class of drug differently.
It is important to iterate that regardless of the prescription
or the OTC status of a product, the requirements for
compliance with the cGMP apply equally.
10. OTCmonograph status is anew section added to theOTC
volume and this should allow manufacturers to chose appropriate
formulations that may not require a filing with
the regulatory agencies; it is important to iterate that an
approved OTC monograph includes details of formulation
including the types and quantities of active drug and
excipients, labeling, and presentation. To qualify the exemption,
the manufacturer must comply with the monograph
in its entirety. However, subtle modifications that
are merely cosmetic in nature and where there is an evidence
that the modification will not affect the safety and
efficacy of the products can be made but require prior
approval of the regulatory agencies and generally these
approvals are granted.
11. Expanded discussion on critical factors in the manufacturing
of formulations provided; from basic shortcuts
to smart modifications now extend to all dosage forms.
Pharmaceutical compounding is one of the oldest professions
and whereas the art of formulations has been
vi Preface to the Series—Second Edition
relegated to more objective parameters, the art nevertheless
remains. An experienced formulator, like an artist,
would know what goes with what and why; he avoids
the pitfalls and stays with conservative choices. These
sections of the book present advice that is time tested,
although it may appear random at times; this is intended
for experienced formulators.
12. Expanded details on critical steps in the manufacturing
processes provided but to keep the size of the book manageable,
and these are included for prototype formulations.
The reader is advised to browse through similar
formulations to gain more insight. Where multiple formulations
are provided for the same drug, it intended to
show the variety of possibilities in formulating a drug
and whereas it pertains to a single drug, the basic formulation
practices can be extended to many drugs of same
class or even of diversified classes. Readers have often
requested that more details be provided in the Manufacturing
Direction sections. Whereas sufficient details are
provided, this is restricted to prototype formulations to
keep the size of the book manageable and to reduce redundancy.
13. Addition of a listing of approved excipients and the level
allowed by regulatory authorities. This new section allows
formulators a clear choice on which excipients to
choose; the excipients are reported in each volume pertaining
to the formulation type covered. The listing is
drawn from the FDA-approved entities. For the developers
of an ANDA, it is critical that the level of excipients be
kept within the range generally approved to avoid large
expense in justifying any unapproved level. The only category
for which the listing is not provided separately is
theOTCvolume since it contains many dosage forms and
the reader is referred to dosage form–specific title of the
series. The choice of excipients forms keeps increasing
with many new choices that can provide many special
release characteristics to the dosage forms. Choosing correct
excipients is thus a tedious exercise and requires sophisticated
multivariate statistical analysis. Whereas the
formulator may choose any number of novel or classical
components, it is important to know the levels of excipients
that are generally allowed in various formulations
to reduce the cost of redundant exercises; I have therefore
included, as an appendix to each volume, a list of all
excipients that are currently approved by the U.S. FDA
along their appropriate levels. I suggest that a formulator
consult this table before deciding on which level of
excipient to use; it does not mean that the excipient cannot
be used outside this range but it obviates the need
for a validation and lengthy justification studies in the
submission of NDAs.
14. Expanded section on bioequivalence submission was
required to highlight the recent changes in these requirements.
New entries include a comprehensive listing
of bioequivalence protocols in abbreviated form as approved
by the U.S. FDA; these descriptions are provided
in each volume where pertinent. To receive approval
for an ANDA, an applicant must generally demonstrate,
among other things, equivalence of the active ingredient,
dosage form, strength, route of administration and
conditions of use as the listed drug, and that the proposed
drug product is bioequivalent to the reference
listed drug [21 USC 355(j)(2)(A); 21 CFR 314.94(a)]. Bioequivalent
drug products show no significant difference in
the rate and extent of absorption of the therapeutic ingredient
[21 U.S.C. 355(j)(8); 21 CFR 320.1(e)]. BE studies are
undertaken in support of ANDA submissions with the
goal of demonstrating BE between a proposed generic
drug product and its reference listed drug. The regulations
governing BE are provided at 21 CFR in part
320. The U.S. FDA has recently begun to promulgate
individual bioequivalence requirements. To streamline
the process for making guidance available to the public
on how to design product-specific BE studies, the
U.S. FDA will be issuing product-specific BE recommendations
(www.fda.gov/cder/ogd/index.htm). To make
this vital information available, an appendix to each
volume includes a summary of all currently approved
products by the U.S. FDA where a recommendation on
conducting bioequivalence studies is made available by
the U.S. FDA. When filing an NDA or an ANDA, the
filer is faced with the choice of defending the methods
used to justify the bioavailability or bioequivalence
data. The U.S. FDA now allows application for waiver
of bioequivalence requirement; a new chapter on this
topic has been added along with details of the dissolution
tests, where applicable, approved for various
15. Dissolution testing requirements are included for all
dosage forms where this testing is required by the FDA.
Surrogate testing to prove efficacy and compliance is getting
more acceptance at regulatory agencies; in my experience,
a well-designed dissolution test is the best measure
of continuous compliance. Coupled with chapters
on waivers of bioequivalence testing, this information on
dissolution testing should be great value to all manufacturers;
it is recommended that manufacturers develop
their own in-house specifications, more stringent than
those allowed in these listings and the USP.
16. Best-selling products (top 200 prescription products) are
identified with an asterisk and a brand name where applicable;
in all instances, composition of these products is
provided and formulation of generic equivalents. Despite
the vast expansion of pharmaceutical sales and shifting
of categories of blockbuster drugs, basic drugs affecting
gastrointestinal tract, vascular system, and brain remain
most widely prescribed.
17. Updated list of approved coloring agents in the United
States, Canada, European Union, and Japan is included
to allow manufactures to design products for worldwide
18. Tablet-coating formulations that meet worldwide requirements
of color selection are included in the Volume
1 (compressed solids) and Volume 5 (OTC) because these
represent the products often coated.
19. Guidelines on preparing regulatory filings are now dispersed
throughout the series depending on where these
guidelines are more crucial. However, the reader would,
as before, need access to all volumes to benefit from the
advice and guidelines provided.
As always, comments and criticism from the readers are
welcomed and these can be sent to me at Niazi@pharmsci
.com or Niazi@niazi.com. I would try to respond to any inquiries
requiring clarification of the information enclosed in
I would like to express deep gratitude to Sherri R. Niziolek
and Michelle Schmitt-DeBonis at Informa, the publisher of
Preface to the Series—Second Edition vii
this work, for seeing an immediate value to the readers in
publishing the second edition of this book and allowing me
enough time to prepare this work. The diligent editing and
composing staff at Informa, particularly Joseph Stubenrauch,
Baljinder Kaur and others are highly appreciated. Regardless,
all errors and omissions remain altogether mine.
In the first edition, I had dedicated each volume to one of
my mentors; the second edition continues the dedication to
these great teachers.
Sarfaraz K. Niazi, Ph.D.
Deerfield, Illinois, U.S.A