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410 Cobert’s Manual of Drug Safety and Pharmacovigilance
“A Ribavirin Pregnancy Registry has been
established to monitor maternal-fetal out-
comes of pregnancies in female patients and
female partners of male patients exposed to rib-
avirin during treatment and for 6 months fol-
lowing cessation of treatment. Physicians and
patients are encouraged to report such cases
by calling 1-xxx-xxx-xxxx” (Package Insert for
PegIntron).”
The area of female exposure to drugs or teratogenic
effects from male partners taking the drugs requires sig-
nificant additional study. However, the methodology for
such work is and will remain exceedingly difficult.
Other Resources
From a practical point of view, the critical issue for
healthcare practitioners, consumers, and health author-
ities is to determine what drugs may be safely taken
before and during pregnancy (including the weeks after
conception and before diagnosing the pregnancy) and
lactation.
perinatology.com
perinatology.com is an excellent website. This site has
multiple links as well as information on specific drugs,
their effects in the various trimesters (if known), lacta-
tion information, neonatal AEs, and a literature search.
Teratology Registries
and Organizations
Given the scarcity of information, it is now recognized
that tracking the pregnancy and its outcome in women
who have taken products either accidentally (not know-
ing they were pregnant) or knowingly is an important
way to understand the potential toxicity (and efficacy)
of drug products.
OTIS — The Organization of Teratology Informa-
tion Specialists (OTIS) is the professional scientific
society made up of the experts that provide the
MotherToBaby service and the researchers that con-
duct MotherToBaby Pregnancy Studies. OTIS was
established in 1987 as a way of connecting experts
in the field of birth defects research to the general
public. OTIS has a call routing system so that any-
one in the United States and Canada can be routed
to an affiliated service to speak with an expert. They
have “MotherToBaby Fact Sheets” which summarize
the available scientific information to determine
whether or not parents and their developing babies
are at risk because of an exposure in their environ-
ment. See: https://mothertobaby.org/about-otis/
A European counterpart is the European Network of
Teratology Information Services (ENTIS — https://
www.entis-org.eu/.
EUROCAT (https://eu-rd-platform.jrc.ec.europa.eu/
eurocat_en) is a large European network of popula-
tion-based registries grouped geographically for the
epidemiologic surveillance of congenital anomalies;
Full, Associate, and Affiliate Members contribute
data with various levels of granularity. As of 2023
multiple registries in 21 countries survey nearly
1.5 million births a year (25% of EU births)/. One
center of particular interest is the Swedish Medi-
cal Birth Registry, at, which is a part of the Centre
for Epidemiology at the National Board of Health
and Welfare in Sweden. What makes this center of
unique interest is that it aims to collect prospective
gestation and pregnancy data on almost all births in
Sweden — between 86,000 and 120,000 per year.
Data collected include information on previous
gestation, smoking habits, medication, family situ-
ation, hospital, length of gestation, type of delivery,
diagnoses of mother and child, operations, type of
analgesia, sex, weight, length, size of head, birth
conditions, place of residence, nationality, and out-
come, delivery, and infant information. There are
also various teratology and mutagenicity societies
around the world in the pharmaceutical and chem-
ical industries, among others.
As regards lactation, the LactMed web site is well
designed and easy to use (https://www.ncbi.nlm.nih.gov/
books/NBK501922/. To this end, many health agencies
around the world now urge or require pharmaceutical
Pregnancy and Lactation 411
companies, hospitals, and so on to track all known
pregnancies.
Finally, the extraordinary and tragic situation with
DES deserves mention here. The possibility that inges-
tion of a drug during pregnancy could produce an AE
years later in the patient or even the offspring is a chal-
lenge to medical research that does not seem solvable
with the existing state of the art.
Frequently Asked Questions
Q: What about the more complex areas of
drug–drug, drug–food, or drug–alcohol inter-
actions in the pregnant and lactating woman?
A: This is really an unknown area. Because gold-
standard, prospective, blinded studies are rare to impos-
sible with pregnant women, data are difficult to obtain
even in the “simpler” situations of a single drug taken
by a pregnant woman. The complexities of interac-
tions, particularly with agents known to be toxic (e.g.,
alcohol) are not able to be studied adequately (if at all)
at this time. The critical issue is the inability to test
hypotheses other than those suggested by epidemio-
logic studies. That is the state of the art today.
Q: Is there not a paradox of sorts here? If a drug
that is known to be harmful to the mother or
fetus but the registry still shows some women
taking the drug, doesn’t that show the fail-
ure of the warning and the risk management
program?
A: Indeed, a successful risk management program, or
REMS/RMP, to avoid pregnancies with a known terato-
gen will theoretically make the registry unnecessary and
undoable. It is one of the tragedies in medicine today
that women who are pregnant knowingly or unknow-
ingly take drugs that are clearly known to be teratogens.
Much more attention is now being paid to risk manage-
ment programs to prevent pregnancies in women taking
these drugs. Whether this will be successful remains to
be seen. This is an area of public health that also requires
“good pregnancy behavior” by the mother (and father)
in terms of smoking, alcohol, eating, medications, and
drugs (both licit and illicit).
Q: Can we quantify the risk when a drug has
been taken by a woman during her pregnancy?
A: When a drug is identified as “teratogenic”, it fortu-
nately does not mean the risk of harm is 100%. The per-
centages vary across time since conception, drugs, dose
period of exposure, and other environmental factors.
As an example, a “major” risk with thalidomide means
20–25%. For each pregnant woman, a decision is to be
taken depending on the indication, the drug, the dose,
the period of exposure, etc.
Q: Which textbooks are the best references
on drug exposure during pregnancy and
lactation?
A: Many … but try the three edited by Briggs, Schae-
fer and Ste Justine for pregnancy and Hale for lacta-
tion. Keep in mind however, that there is often a lag
between the writing of a textbook and its publication
(including this Manual!). Textbooks also go out of date
as new information is amassed. So, one should also refer
to online resources in addition to published (paper)
textbooks.
Q: It seems there is a dearth of evidence-based
information to support decision-making in
this area. What is the direction of research?
A: We are in an exciting age where science is evolv-
ing and new medical technologies continue to emerge.
Some of these that may be important in generating new
information for women’s health include nanotechnol-
ogy, pharmacogenomics, novel imaging technologies
and methods, 3D printing, and developments in regen-
erative medicine. Incremental progress in these areas
should spawn new methods and tools for evaluating
sex and gender factors related to the use of medicines.
Indeed, advancing research should support develop-
ment of innovative products and technologies for bet-
ter management of medicines used in the healthcare of
women.
CHAPTER
413
39
Product Quality Issues
A
dverse events are not the only
issues of concern when it comes
to monitoring the safety of a
product. Product issues due to manu-
facturing, quality control, challenges
with the packaging or labeling, storage,
tampering, counterfeiting, sterility,
impurities, contamination, and so on,
can also lead to risks associated with
product use. The public health impli-
cations of poor quality control of prod-
uct in all stages of manufacturing lend
to the important of understanding the
critical link between functions such as
Quality, Manufacturing, Labeling, etc.
and Safety & Pharmacovigilance. This
chapter summarizes briefly issues that
revolve around quality and manufac-
turing as it relates to concepts within
pharmacovigilance.
Introduction
Issues in addition to bad reactions to the active chemi-
cal entity in the product play a significant role in drug
safety and pharmacovigilance because of the realiza-
tion that a safety issue may be related to more than
just the active ingredient (active moiety). Excipients,
residues from the manufacturing process, quality con-
trol (or lack thereof), the container and packaging,
storage issues in the pharmacy or home, tampering,
counterfeiting, and other misadventures that occur
before and after the product has left the factory can
produce bad effects. So, an adverse event (AE) can be
more than just a bad reaction to the active chemical
entity.
414 Cobert’s Manual of Drug Safety and Pharmacovigilance
How did we get here? In 1955, more than 200,000
children received a polio vaccine in which the process
of inactivation of live virus proved to be defective.
Within several months, about 40,000 cases of polio had
occurred; 200 children had various degrees of paralysis
and 10 died from poliomyelitis.
1
Fortunately, most of
the frequently seen product quality issues do not gener-
ate such serious safety concerns.
Basics
What is a product quality issue? What is a Product Quality
Complaint? What is a Medication Error? There are a few
definitions available for reference in regional regulations
and ICH, however in general a Product Quality Complaint
(PQC) is any written, electronic or verbal communica-
tion regarding the failure of, or defect, in a drug product
(either real or perceived) to meet any of its specifications
or standards of quality, purity, identity, safety or potency.
Similarly, there are medication errors which are any pre-
ventable events that may cause of lead to inappropriate
medication use or patient harm while the medication is
in the control of a Health Care Professional, patient, or
consumer. Medication Errors (MEs) can include incor-
rect route/formulation, improper dosage (including
overdose/underdose), incorrect dosing schedule or fre-
quency, an incorrect medicinal product administration,
such a mix-up of drug names or accidental administer-
ing a contraindicated subgroup such as to children, and
accidental/unintended exposures to the product.
The FDA defines a Drug Product Complaints as “...
involving the possible failure of a drug product to meet
any of its specifications and for such drug products, a
determination as to the need for an investigation in
accordance with 211.192” (21 CFR 211.198). Addi-
tionally, 21 CFR 211.192 incorporate further guidance
regarding the Product Complaint Review, stating “All
drug production and control records, including those for
packaging and labeling, shall be reviewed and approved
by the Quality Control Unit to determine compliance
with all established, approved written procedures before
a batch is released or distributed”. When a drug product
1
The cutter incident: How America’s first polio vaccine led to a
growing vaccine crisis, J R Soc Med. 2006; 99(3): 156.
or its packaging fails its specifications at a clinical site
or by an investigator, then it should be considered a
complaint.
Below are some examples of PQCs. It is important
that a company establishes their own list of PQCs specific
to the product type and known or anticipated/potential
complaints, concerns, or failures. These, as stated above
and as per regulations, should be described in SOPs and
provided in regular training materials to employees.
1. Package Integrity (Container broken, stopper/
seal not intact, stopper difficult to penetrate, etc.)
2. Suspected counterfeit/falsified product
3. Label/Labeling missing or errors
4. Discolored product
5. Patient preference (color, small, funny/odd
taste, bad taste, metalic taste after injection,
burns upon injection, etc.)
6. Lack of Efficacy for labelled indication (also
should be an AE)
7. Evidence of product tampering
8. Particulate or foreign matter
9. AE associated with a specific batch which was
not experienced with other batches (also report
as AE)
10. Patient or healthcare professional product com-
plaints can revolve around the following:
The drug did not work (lack of efficacy);
The drug produced an adverse event (AE)
(safety issue);
The drug looked, tasted, or smelled funny or
different. It was crumbling. There was a pow-
der on the pill and so forth (product manu-
facturing or quality issue);
The drug was a tablet in the past, but this
time it was capsules (quality issue in packag-
ing, dispensing, etc.);
I want my money back or I am going to sue;
I ordered these pills on the Internet from a
pharmacy supposedly in Canada (possible
counterfeit or quality issue);
I saw on the Internet that this pill should....;
or
Others (“My dog accidentally ate the pills”).
Product Quality Issues 415
Frequently, one sees multiple issues with a single
phone call: “The pill was the wrong color, and when I
took it, I developed chest pain, and I want my money
back or I’ll sue.” Part of the issue here involves getting
the correct people within the pharmaceutical company
(or health authority or call center if they are the first to
receive the call) to act on each of the issues involved:
the AE component, the product quality component,
and the monetary/legal component. In this chapter, we
address product quality issues.
Manufacturing Considerations
Manufacturing is regulated in most countries and
regions by a set of regulations, directives, laws, and
guidances that go under the general rubric of “Good
Manufacturing Practices”, or GMP. The International
Conference on Harmonization (ICH) has addressed
manufacturing issues in a series of “Quality Guide-
lines”, covering such topics as stability, analytical val-
idation, impurities, and so forth. The key document
is Q7: Good Manufacturing Practices which has been
adopted/implemented in the EU, the USA, Canada,
Japan and Switzerland, along with a Q&A that was
published on June 10, 2015, which clarified several
sections of the Q7 Guideline. Since then, each country
or region has enacted its own requirements for GMP.
Additional countries beyond the original adopters
have now integrated the ICH Q7 Guideline into local
requirements.
In the United States, in the Code of Federal Regu-
lations Part 211 (21CFR211) Current Good Manu-
facturing Practice for Finished Pharmaceuticals.
The European Union published its new Directive
for pharmaceutical manufacturing sites that has
replaced the existing Directive (Directive 2003/94/
EC) for human medicines. The new EU GMP Direc-
tive, (EU) 2017/1572, was issued on September 15,
2017 and became law by March 31, 2018.
To a large degree, the GMP requirements are quite
similar around the world, and one factory will fre-
quently produce products sold in many (or all) global
markets, thus meeting all standards.
In the United States, the specific section covering
product quality issues is 211.198 Complaint Files:
“(a) Written procedures describing the han-
dling of all written and oral complaints
regarding a drug product shall be established
and followed. Such procedures shall include
provisions for review by the quality control
unit, of any complaint involving the possible
failure of a drug product to meet any of its
specifications and, for such drug products,
a determination as to the need for an inves-
tigation in accordance with Sec. 211.192.
Such procedures shall include provisions for
review to determine whether the complaint
represents a serious and unexpected adverse
drug experience which is required to be
reported to the Food and Drug Administration
(21CFR211.198).”
This section obliges the manufacturer to maintain
written procedures on the handling of all complaints
and specifies that a review must be done for serious
and unexpected AEs. The US FDA performed a total of
5,615 GMP inspections of registered drug and device
domestic and foreign establishments in 2015 (FDA
2016 Annual Report on Inspections of Establishments
in FY 2015). Product quality issues are often cited.
An example follows from a Warning Letter to a phar-
maceutical company in December 2017. Note that
Warning Letters are usually sent to the CEO of the
company:
1. “This warning letter summarizes significant vio-
lations of current good manufacturing practice
(CGMP) regulations for finished pharmaceuti-
cals. See 21CFR, parts 210 and 211.
2. “Because your methods, facilities, or controls for
manufacturing, processing, packing, or holding
do not conform to CGMP, your drug products are
adulterated within the meaning of section 501(a)
(2)(B) of the Federal Food, Drug, and Cosmetic
Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).”
3. “We reviewed your (date) response in detail.”
416 Cobert’s Manual of Drug Safety and Pharmacovigilance
4. During our inspection, our investigators observed
specific violations including, but not limited to,
the following.
5. “Your firm failed to thoroughly investigate any
unexplained discrepancy or failure of a batch or
any of its components to meet any of its speci-
fications, whether or not the batch has already
been distributed (21CFR211.192).”
6. “You failed to thoroughly investigate release and
stability testing failures concerning two batches
of your drug products. These product failures
included viscosity and appearance. During stabil-
ity testing, you also identified packaging defects.
You did not initiate investigations for each of
these drug quality issues. When you did investi-
gate, you failed to adequately evaluate the manu-
facturing process and associated records, identify
root causes, and implement effective corrective
actions and preventive actions (CAPA).”
The responsibility for investigating product com-
plaints generally falls within the competence of one of
the quality units in a company. The drug safety depart-
ment usually becomes involved when there is a product
quality complaint (PQC), a medication error, or an AE
associated with a PQC. That is, even though there was
an issue with the manufacturing or quality of the prod-
uct, the subject took the product and had an AE. Some-
times, of course, the quality issue is only discovered or
noted after the use of the product (e.g., the patient had
an AE and went back to look at the package and noted
the tablets smelled funny and were off-color a quality
issue).
Within the pharmaceutical company, this is a “dou-
ble issue”, with an evaluation of the AE by the drug
safety group and an evaluation of the product com-
plaint by the quality unit and the manufacturing unit
concerned. There are several critical operational issues:
All units (e.g., drug safety, manufacturing, and qual-
ity control) must be informed that the other units
are involved in the same case if it was received and
triaged elsewhere (e.g., in Medical Affairs or Medical
Communications). Each unit follows its procedures
and does its evaluation, usually simultaneously.
The units must communicate their findings to each
other because one or both will likely be required
to submit the findings to the health authorities.
A mechanism must be developed to request that the
patient who filed the complaint return any unused
product to the company for analysis. Some compa-
nies do this for all complaints, whereas others set
up specific criteria for requests for return of the
product. The quality workup may include review-
ing batch records, testing the retained sample, and
testing the sample returned by the patient.
The results of this testing must be conveyed to
the drug safety unit to include in the report to the
FDA and any other concerned health authorities.
If this is an expedited report, the quality unit must
get the new information to the drug safety unit so
that the follow-up to the agencies is done within
the required time (often 15 calendar days or less for
serious/urgent issues). The quality unit must not
delay sending the information to the drug safety
group. Similarly, relevant clinical follow-up infor-
mation (e.g., lot numbers) from the drug safety unit
should be forwarded immediately to the quality
unit on the case.
The case may have two or more different identifi-
cation numbers, one in the drug safety unit and the
other in the quality unit. If the computer system(s)
cannot handle the two numbers for the same case,
then another method of tracking must be devel-
oped to ensure that the case does not fall through
the cracks. For large companies, the volume of such
investigations may be quite high, with many data
flowing back and forth between the departments. In
addition, a third or even fourth department may be
involved if the case involves a refund of money to
the patient or a possible legal or police action (e.g.,
a lawsuit or police investigation for tampering).
Now that the manufacture of many products is
outsourced and sometimes done in more than one
factory (e.g., one for raw materials and another for
finished product and packaging), coordination and
investigation may become complex and require
careful and meticulous coordination and tracking.
AEs and product quality complaints are now con-
sidered “two sides of the same coin”. That is, if
an AE occurs after taking a drug, it is not always
Product Quality Issues 417
evident that the event is due to the active ingredi-
ent. It might be due to an excipient or a problem
in manufacturing, storage, or shipping, or perhaps
the product is a counterfeit. It is good pharma-
covigilance practice for the drug safety group or the
pharmacovigilance or risk management group to
examine product quality issues on a regular basis
to determine whether a clue or suggestion indicates
that quality issues have produced AEs. The method-
ology for this evaluation (the relationship of quality
issues to AEs) has not been fully harmonized yet
and remains a methodology of “global introspec-
tion”. Some of the newer transactional safety data-
bases are now able to capture product quality issues
for cases in addition to the usual AE data. The anal-
ysis should attempt to see whether there are similar
cases (AEs and product complaints) seen with that
product’s lot, batch number, or geographic area.
Mail-order pharmacy systems distributing drugs
from centralized locations to all parts of the United
States now make geographic tracking much harder
and less useful. The days when a particular batch
of a drug was used in a localized geographic area
are disappearing in the United States but less so in
smaller countries or regions.
Many of the AE/product quality issues are often
small and non-critical. Examples include the dis-
covery that a part of the packaging (e.g., vials or
stoppers) was obtained from a new vendor and
looked or acted differently, or late stability testing
showed problems. Sometimes it is discovered that
a part or procedure was slightly but clearly out of
specification. The determination of how far to pro-
ceed in terms of analysis and recall of products is
often a difficult decision that requires the assistance
of multiple departments within the company and
the concerned health agencies. Complications can
arise if one health agency wants or demands a recall
and another does not. A formal written procedure
must be developed and used.
Note: In the EU as well as in Japan, reports of infec-
tions in patients who used an injectable drug must be
considered serious and managed as a safety signal. In
the United States, this would be considered a manufac-
turing issue.
Product Recall
Significant and severe product quality issues, in partic-
ular those that risk patient health or produce serious
AEs or suggest tampering, must be acted on immedi-
ately. The pharmaceutical company must have a mech-
anism in place to recognize such issues, investigate
them, and bring the information to the responsible lev-
els of the company and the health agencies in a timely
fashion. If necessary, a product may need to be with-
drawn immediately, public and internet/social media
announcements made, protocols stopped, and so forth.
The company should have a procedure whereby the
team that would need to perform these actions is easily
mobilizable for action. It is also a PV role to identify
safety signals due to quality defects.
The definitions of recalls and withdrawals in the
United States are as follows:
Class I recall: This is a situation in which there is
a reasonable probability that the use of or exposure
to a violative product will cause serious adverse
health consequences or death.
Class II recall: This is a situation in which use of
or exposure to a violative product may cause tem-
porary or medically reversible adverse health conse-
quences or where the probability of serious adverse
health consequences is remote.
Class III recall: This is a situation in which use
of or exposure to a violative product is not likely to
cause adverse health consequences.
Market withdrawal: This occurs when a prod-
uct has a minor violation that would not be subject
to FDA legal action. The firm removes the prod-
uct from the market or corrects the violation. For
example, a product removed from the market due
to tampering, without evidence of manufactur-
ing or distribution problems, would be a market
withdrawal.
Medical device safety alert: This is issued in
situations in which a medical device may present
an unreasonable risk of substantial harm. In some
cases, these situations are considered recalls. Exam-
ples of recalls, withdrawals, and safety alerts can be
seen at the FDA’s website.
418 Cobert’s Manual of Drug Safety and Pharmacovigilance
Recent examples are provided as follows:
Cracked glass at the rim surface of the vials;
Product mix-up;
Potential microbial contamination which compro-
mises sterility or lack of sterility assurance;
Potential serious side effects;
Mislabeling;
Presence of particulate matter;
Presence of glass particles;
Violations of current good manufacturing practice
regulations;
Contains dexamethasone instead of hydrocortisone;
Unapproved drug;
Potential for product to be below specification; or
Missing expiry/lot information.
Generally, most countries have mechanisms for
emergency recalls or withdrawals from the market of
products that have severe or dangerous or high-risk
quality problems. This may be for the entire drug or
only for certain formulations, lots, or other subgroups.
These may be handled as expedited, reports or “rapid
alerts” using the Rapid Alert Procedure in the Euro-
pean Union. Although the safety group may be closely
involved, the operational issues of the withdrawal or
alert will involve multiple groups, including manufac-
turing, regulatory, legal, and communications (if the
public has to be contacted).
Counterfeiting & Falsified
Products
Counterfeit, fake, specious products are now a major
concern. This is especially true for certain high-margin,
highly desired drugs on the market (e.g., erectile dys-
function drugs, narcotics). Many companies and health
agencies are confronting this issue. Warnings are issued
almost weekly by health agencies to consumers and
medical personnel regarding fake products that can be
harmful to patients.
In 2011, FDA issued a guidance on mechanisms
companies can implement to identify counterfeit prod-
ucts: Incorporation of Physical–Chemical Identifiers into
Solid Oral Dosage Form Drug Products for Anticounter-
feiting. This was followed by another FDA guidance
document in 2016 titled, Drug Supply Chain Security
Act Implementation: Identification of Suspect Product and
Notification Guidance for Industry.
See also the World Health Organization’s informa-
tion on drug counterfeiting.
In the European Union, “falsified medicines” are
not the same as “counterfeit medicines”. A counterfeit
medicine is a medicine made by someone other than
the genuine manufacturer, by copying or imitating an
original product without authority or rights. Counter-
feit medicines infringe trademark law. In contrast, a fal-
sified medicine is a fake medicine that is designed to
mimic a real medicine. Falsified medicines do not pass
through the usual evaluation of quality, safety and effi-
cacy that is required for an EU authorization procedure.
Every company marketing or distributing a prod-
uct should have an SOP dealing with counterfeit or sus-
pected counterfeit products. It should set up procedures
for drug safety, corporate quality/manufacturing, legal,
and regulatory to deal with matters in their domains.
The manufacturing/quality groups should determine
that the product is fake, ideally by requesting that it be
sent to the company (in a postage-free mailer) for eval-
uation and testing.
Unfortunately for drug safety, the case usually
arrives as a “normal” SAE or non-serious AE and must
be handled as such even if it is suspected to be from
a counterfeit medication. Such suspicions should be
noted in the narrative of the initial report, if present,
and a note made that follow-up verification is being
pursued. The physical product should be requested
immediately, including the packaging, and forwarded to
manufacturing/quality for testing upon receipt. Obvi-
ously, all communications and receipt must be well doc-
umented in the database.
If a case turns out to be due to a counterfeit and not
due to the company’s product, this should be notified in
a follow-up to all concerned health authorities. How it
is handled in the database in periodic reports (PSURs)
is tricky and not standardized. As a rule, the case should
not be included (necessarily) in the tables, listings, and
analyses of the company’s product, but rather addressed
Product Quality Issues 419
in a separate section of the report. It may be difficult
to handle this within the safety database. Drug safety
may want to work with the legal and regulatory depart-
ments as well as manufacturing to set up a coordinated
system to handle this. Some companies are now setting
up security departments just to deal with counterfeits.
Safety databases should be updated to manage such AE
reports from suspected/confirmed/disproved counter-
feit (or falsified) products. This issue actually increases
dramatically in many countries (Africa, Asia among
others).
General Remarks
This chapter is not the end of the discussion regarding
PQCs, MEs, counterfeiting, falsified products and other
GMP/GVP concerns. This should just be the beginning.
Companies should have the appropriate qualified staff
in place who can have enough foresight to ensure pro-
cesses are in place to handle these situations even if
their occurrence in some instances is remote. It is also
important for employees in pharmacovigilance, quality,
manufacturing and labeling to be trained in GMP reg-
ulations and fully understand the human/public health
implications should some of these events occur and go
on unaddressed and uncorrected. Ask yourself these
questions:
1. Do you have these events defined within your
organization?
2. Are you able to collect and report on these
types of events? Is there a database or a means
to collect and store, then analyze and report on
these events?
3. Do you have procedures in place to cover these
topic areas?
4. Is your company able or equipped to handle a
product recall in reaction to a PC/PQC or other
manufacturing issues?
5. Is there training available in your company
regarding these topics?
If you can’t answer these questions, hire an exter-
nal consultant who can help setup these processes and
assist in evaluating the established system for quality
and compliance purposes.
Frequently Asked Question
Q: This doesn’t seem fair. Why should a
company have to report and waste time and
resources on tracking down safety matters
concerning counterfeit drugs?
A: Well, of course, life is not fair. But this is still an
important public health issue and the company will
serve both the public health and its own interest (to
protect its products) by pursuing and resolving issues
around counterfeits. In practice, it is not always clear
whether a drug is or is not a counterfeit, especially if the
original packaging is no longer available. A counterfeit
may present a health threat and, thus, possibly cast a
negative shadow on the true product. Preventing a legit-
imate product from being tarnished by such an assault
should be a priority for the company.