Download Banned Substances in Cosmetic Regulation The EU Example

ADVERSE EVENTS
AND
NON-COMPLIANT PRODUCTS
Presented by
Nazarita T. Lanuza, R. Ph., M. M.
COSMETO-VIGILANCE
Adverse event reporting
and
Causality
Cosmeto-vigilance
● There is no definition worldwide of
cosmeto-vigilance and adverse events on
cosmetics.
● Pharmacovigilance is being done in most
countries
Why Pharmacovigilance?
Pharmacovigilance is the science of
collecting, monitoring, researching and
evaluating data on the effects of medicinal
drugs, biological products, herbals and
traditional medicines with a view to
identifying new information about adverse
reactions and preventing harm to patients.
The information collected during the
pre-marketing phase of a medicinal drug is
inevitably incomplete with regard to
possible adverse reactions:
● Test in animals are insufficiently
predictive of human safety.
● In clinical trials patients are selected and
limited in number, the conditions of use
differ from those in clinical practice and
the duration of trials is limited.
● Information about rare but serious
adverse reactions, chronic toxicity, use in
special groups (such as children, the
elderly or pregnant women) or drug
interactions is often incomplete or not
available
Pharmacovigilance is needed in every
country, because there are differences
between countries (and even within
countries) in the occurrence of adverse drug
reactions and other drug-related problems.
This may be because of differences in:
● Drug production
● Distribution and use (e.g. indication,
dose, availability)
● Genetics, diet, traditions of the people
● Pharmaceutical quality and composition
(excipients) of locally produced
pharmaceutical products
● The use of non-orthodox drugs (e.g. herbal
medicines) which may pose special
toxicological problems, when used alone or
in combination with other drugs.
Pharmacovigilance is needed for the
prevention of drug-induced human suffering
and to avoid financial risks associated with
unexpected adverse effects.
Definition of Adverse Drug Reaction
Any response to a drug which is
noxious and unintended and which occurs
at doses normally used in man for
prophylaxis, diagnosis or therapy of
disease, or for the modification of
physiological function.
● Thalidomide incident in the 1960’s
An adverse reaction may result from effects
of the drug, of illness, and their interaction
with each other. Causality between the
clinical event and the drug may not always
be present although with a reaction (ADR),
causality is more definite. For adverse
reactions during therapy, remember that
they:
●
●
●
●
Are undesirable
Are unintentional
Are suspected (not necessarily proven)
May develop as a consequence of therapy
or other procedures
Key Points in ADR Reporting:
* Identifying rare adverse effects
* Monitoring newly introduced drugs where
their safety profile is relatively unknown
* Hypothesis generating and raising of
signals or flags
* Supporting the regulatory policies in the
promotion of drug safety
* Contributing to improvement in health
policies and practices such as rational
drug prescribing
It should be emphasized that such
reports are neither proof nor admission
of causality. ADR monitoring teaches us
what we do not know and how to
become better healers.
ADR ON
ALLOPURINOL
COSMETO-VIGILANCE
● Cosmetic products are consumer goods
that are basically conceived to make
people feel comfortable and happy after
its use.
● But there are possibilities that the
expected result turns to opposite: it is
called an adverse event.
Some allergic reaction to
cosmetics such as poorly
formulated antiperspirant
COSMETO-VIGILANCE
● An adverse event may be encountered by
consumers in the course or after the use
of cosmetic products and can be
originated by a misuse or by a faulty
product (quality defect).
Skin
reaction

● Adverse effect can also originate from a
physiological reaction to the chemicals
present in the product (health concern).
Some allergic
reaction to
cosmetics such as
beach sunscreen
Skin allergies to a plant (Primula)
Skin reactions to irritants :
exfoliation of hand skin by cleansing
liquid
COSMETO-VIGILANCE
● Products are conceived to be safe for
health when used in normal condition.
Regulation contains many disposition in
that direction.
Some allergic reaction to
cosmetics such as hair dye
COSMETO-VIGILANCE
● But safety studies conducted with
ingredients cannot provide an exhaustive
guaranty of innocuity to all cosmetics for
all consumers.
Testing for allergic
sensitivity, using
progressively more dilute
solutions on forearm skin
COSMETO-VIGILANCE
● Despite important safety precaution, the
use of cosmetic products present on the
market, may some time reveal inadequate
for certain people who are specifically
sensitive to certain chemicals, adverse
effect remains possible on these
consumers.
Skin reactions to irritants : irritated
skin around the eyes, caused by
a poorly formulated cosmetic
product
COSMETO-VIGILANCE
● Regulation trend is to make the
monitoring of adverse effects related to
health of consumers, a mandatory task
for manufacturers.
● In the EU before the 7th amendment of
the cosmetic Directive, there was no
regulatory disposition for the monitoring
of health related adverse effects
generated by products on the market.
COSMETO-VIGILANCE
● Some companies have however set up
their own system allowing the gathering
of such data. Such is also true in the
United States.
● 7th Amendment makes the collection of
information on health adverse effects
mandatory. In addition, companies have
to allow consumers a free access to these
information. Information is limited only
to health related events.
COSMETO-VIGILANCE
● Free access to information are possible by
electronic means (telephone or Internet)
● Collection of information is shared
responsibility of the manufacturer,
regulatory and users
Example of organization set by
companies:
Consumers affected by an adverse event can
have access to company through company
address or <<A Phone Number>> usually
printed on product label. Company receives
and put on record the consumer’s complaint
and other details and redirect the information
to the person in charge of cometovigilance
inside the company.
cont. . . .
The Person in charge of cosmetovigilance
contacts the consumer back (by
visit/phone/mail) and starts an
investigation following a specific
questionnaire in order to classify the type
of effect encountered by the customer, its
causality and the necessity to eventually
have this consumer examined by a
dermatologist.
cont. . . .
Companies set up a network of affiliated
dermatologists is ready to diagnose
specific cases and to inform the company
on the health issues linked to the use of
their products.
COSMETO-VIGILANCE
● Data are collected in a data base and
regularly reviewed.
● In case of a relation linking the adverse
effect to the product composition, the
causality is further investigated.
● Patch test with suspected ingredients in
the product are conducted on consumers
under the supervision of the
dermatologist to help in identifying the
substance that may have caused the
adverse event. Data are fed back to the
Research and Development laboratory of
the company for statistical analysis.
Confirming allergies: the
results of a patch test on
the skin of patients back
Post Marketing Quality Compliance
Programme (PMQCP)
Objectives:
PMQCP involves the active systematic
scientifically valid collection, analysis and
interpretation of data or other information
about a marketed product.
The data can reveal unforeseen adverse
events, the actual rate of anticipated
adverse events or other information
necessary to protect the public health.
Sampling:
The approach shall be based on risk
assessment.
● Adulterated
● Misbranded
Criteria for sampled collection:
● Cosmetic products intended for use
around the eye and genital regions, those
that may come into contact with the
conjunctiva or mucosa respectively.
Criteria for sampled collection:
● Products where certain amount of the
product may be ingested, inhaled or
absorbed through the mucous
membranes such as oral hygiene products
and products used on lips.
● Hair colouring products that may contain
prohibited or restricted colour additives.
Criteria for sampled collection:
● Adulterated or misbranded cosmetic
products. A cosmetic product is
misbranded if its labeling is false or
misleading, if it does not bear the
required labeling information.
Inspection of establishments:
Factors to determine when an inspection is
warranted:
• Type and risk-level of products
• Significance of market information and
feedback from consumer or industry
• Company’s history of compliance
• Regulatory Authority’s surveillance and
compliance activities
Examples of Post Marketing
Surveillance Systems
A few Member States have implemented either a formal or
response-based PMS system that include one or a combination
of the following:
i.
ii.
a market quality surveillance programme,
random and / or systematic checks through sampling of
products from the market and / or from manufacturers and
importers store,
iii. checks in response to Adverse Cosmetic Report
(ACR) or complaints
.
Examples of Post Marketing
Surveillance Systems
The PMS may be connected to a manual or electronicbased ACR reporting System.
Manual System
Electronic System
Voluntary System
*(Non-compliance)
to Pre-Licensing
Adverse Cosmetic
Reaction Reporting
Formal Programme
Post-Marketing
Surveillance
Response-based
Feedback /
Complaints
Safety Alerts
/ Public
Notification
Risk-based
Suspension
Of Sale
*(Batch/Product)
Recall/Withdrawal
Guidelines on Cosmetic Product
Adverse Reporting System
Report
Adverse information on cosmetic products can
be made on prescribed forms, either manually or
electronically. Information on ACR may come
from the following sources:
• Consumer complaints
• Feedback from health professionals
• Product manufacturer and/or importers, .
distributor
• Regulatory Authorities of other countries
• ASEAN ACR Database
Guidelines on Cosmetic Product
Adverse Reporting System
Electronic ACR System
A centralized ASEAN ACR Database to collect
and document adverse reports from each ASEAN
member through an Internet (World Wide Web)
system is recommended.
The advantages and benefits of a centralized
electronic database include the rapid retrieval
of information so that prompt and effective
actions could be taken to protect public health
and safety.
Guidelines on Cosmetic Product
Adverse Reporting System
Electronic ACR System
Information exchange among the regulators in ASEAN is
a key factors in the successful implementation of
PMS/SE. The objectives of the information Exchange
Network include:
a. Provision of a formal process of transfer of
information across ASEAN Member States;
b. Provision of a rapid, accurate and secure channel for
information flow to key regulatory agencies; and
c. Facilitation of regulatory processes and decisions in
each Member State through sharing of regulatory
expertise and ideas.
Guidelines on Cosmetic Product
Adverse Reporting System
cont. . . . . . .
The development and implementation of the information
exchange network may take effect in 2 phases:
Phase 1
A formal but simple system of communication network
arrangement for Immediate implementation with the
following features:
a. Contract points established within each ASEAN
Member State
Guidelines on Cosmetic Product
Adverse Reporting System
cont. . . . . . .
b. Identified scope of regulatory responsibility
c. Types of information to be exchanged
Phase 2
Enhancement of communication network
established in Phase 1 by the hosting of an
Internet-based website database management
system with the following features:
a. Notifications, announcements and reports of
the ASEAN Cosmetic Committee (ACC)
Guidelines on Cosmetic Product
Adverse Reporting System
cont. . . . . . .
b.
Reports on review of new cosmetic ingredients by the ASEAN Cosmetic
Scientific Body (ACSB)
c. Database could be maintained for information on defective cosmetic
products, fraudulent companies, cosmetic products sold in the various
ASEAN countries, GMP Audit reports, etc.
d. Adverse Cosmetic Reaction reports – information uploaded in the
website for rapid dissemination
e. Other trade information such as:
i. ASEAN Cosmetic Directives and new updates
ii. Guidelines (e.g. GMP Guidelines, PMS / SE Guidelines, etc
iii. Test methodology
iv. Cosmetic Ingredients and nomenclature
v. Scientific review of cosmetic products
Guidelines on Cosmetic Product
Adverse Reporting System
cont. . . . . . .
A diagrammatic depiction of the Information Exchange Network is shown
below:
Enquiries
(Products, Dealers
Sharing of Regulatory
Information / Expertise
Information / Alerts on
ACR, Recall, Risks, etc.
Forum on new Regulatory
Initiatives, Projects
Information
Exchange
Network
ASEAN
MEMBER
STATES
Guidelines on Management of Adverse
Information on Cosmetic Products
Evaluation of Adverse Report
On receipt of an adverse report, an evaluation of the health hazard presented
by a cosmetic product shall include but not limited to the following:
•
•
•
•
•
Severe or unusual skin irritation or allergic reaction, eye irritation,
urogenital tract or respiratory tract irritation, or apparent toxicity;
Reports of unusually large numbers of adverse events, even when the event
is less severe;
Mislabelling because they contain unlisted ingredients, lack instructions for
safe use, or lack of any necessary warning statements which may constitute
health hazards;
Suspectec microbiological contamination; or
Exposure to high levels of toxic heavy metals.
Guidelines on Management of Adverse
Information on Cosmetic Products
Outcomes
• Action by the Regulatory Authority:
Each Member State shall have full authority to determine and impose the
remedial actions and legal penalties under the situation of product noncompliance of the company to the requirements of the ASEAN Cosmetic
Directives.
• Withdrawal or suspension of sale:
Remedial actions shall include mandatory and voluntary removal / suspension
from sale by a company. The removal / suspension may be either a permanent
or temporary removal of the affected product from the market for product
correction, after which the corrected product may be returned to the market
use.
Guidelines on Management of Adverse
Information on Cosmetic Products
Cont . . . . . .
• Issuance of safety alert / product notification:
The company may be required to provide advice to the public regarding a
specific situation with respect to a product which, while performing to meet all
specifications and therapeutic indications, might present an unreasonable risk of
substantial harm if certain specified precautions in regard to its use are not
observed.
• Recall
A recall may either be a permanent removal of the affected products from the
market or a temporary removal for product correction, after which the
corrected products are returned to the market for use. The type of recall to be
initiated will depend on the nature of the defect involved.
Guidelines on Management of Adverse
Information on Cosmetic Products
Cont . . . . . .
The information to be provided should include but not limited to the following:
a)
Details of Defect
• Date of occurrence of defect
• Nature of defect
• Cause of defect
• Number of occurrence of similar defects
• Results of tests or investigations on suspected products or other products
• Assessment of risk to user
• Proposed action by Company (in the local and ASEAN markets, where
product is sold)
• Proposed recall classification
• Proposed recall level
• Other relevant details
Guidelines on Management of Adverse
Information on Cosmetic Products
Cont . . . . . .
b)
Details of Defective Product
• Product name and its description, including strength, dosage form, pack
size and identification number, if applicable
• Batch number
• Expiry date
• Manufacturer
• Country of manufacture
• *(Quantity manufactured/imported)
• *(Quantity sold, quantity of stocks held)
• *(Quantity recalled from market (submitted after consolidation of recall
report)
Guidelines on Management of Adverse
Information on Cosmetic Products
Cont . . . . . .
c) Details of Manufacturer / Product Owner /
Company Responsible
• Name of Company
• Name of person responsible
• Telephone No. / Fax No. of person
responsible
Guidelines on Management of Adverse
Information on Cosmetic Products
• Assessment of Recall
The recall classification and recall level are
determined by consultation between the
Company and the Regulatory Agency.
a) Recall Classification
Class 1 recall
This is initiated when the problem or defect
poses a life-threatening situation to users.
Class 2 recall
This is initiated when the problem or defect
is unlikely to cause serious harm to users.
Guidelines on Management of Adverse
Information on Cosmetic Products
• Responsibilities of Manufacturer / Product Owner
The manufacturer / product owner has responsibility in the following 2 areas:
• Maintain sales records and establish proper procedures for effective recall of
product in the event that such action becomes necessary; and
• Take the prime responsibility in carrying out the product recalls, including
notification of recall to all affected parties, recovery of product, institution of
corrective action and implementation of follow-up checks to ensure that
recalls are successful and completed.
a)
Records
The manufacturer / product owner must maintain and keep relevant records, to
enable prompt and effective recall of affected products. All records should be
readily to the Regulatory Authority available so as to expedite recall when
necessary.
Guidelines on Management of Adverse
Information on Cosmetic Products
cont . . . . . .
a)
Implementation of Recall
When there is a recall initiated, the manufacturer / product owner should
immediately place an embargo on the remaining stock of the product and notify
all its customers to do likewise pending further investigation.
Recall letters to be sent out by manufacturer / product owner should contain
factual information on the defective product. They should include but not
limited to the following:
•
•
•
•
Name of defective product
Active ingredients and strength
Pack size
Dosage form
Guidelines on Management of Adverse
Information on Cosmetic Products
cont . . . . . .
•
•
•
•
•
•
•
•
•
Batch number
Manufacturer / Country of manufacture
Other details for easy identification
Reason(s) for recall – nature and cause of defect
Assessment of risk to user
Necessity to identify, cease sale and quarantine product
Method of recovery / collection of defective product by company
Date of recall letter
Name of person and company responsible and the contact numbers for
inquiry
• Signature of person responsible for the recall
If the hazard to user is serious, indication of clinical symptoms and advice to
consult a medical practitioner is warranted to be included in the recall letter.
Guidelines on Management of Adverse
Information on Cosmetic Products
cont . . . . . .
When there is a risk of significant hazard to consumers and the distribution has
been extensive, the manufacturer / product owner responsible is required to
employ all possible mass communication media available including newspaper,
radio and television broadcast to disseminate the recall information to the
consumers.
The manufacturer / product owner is also responsible for recovering the
defective product from all affected parties, instituting corrective actions, if
necessary and ensuring that the product recall is completed.
The manufacturer / product owner is required to submit a final report to the
Regulatory Authorities of the country where the product is marketed, upon
completion of the recall.
Guidelines on Management of Adverse
Information on Cosmetic Products
• Conclusion
Manufacturers, product owners and sellers are
responsible for the quality, safety and efficacy
of their products. All efforts must be made to
ensure that recall operations are carried out as
efficiently and effectively as possible.
Appropriate follow-up actions must also be
taken to prevent future recurrence of similar
problem.
Example of Defective Products
Notification Form
I. Company Particulars
Name of Company
Person Responsible
Tel. No.
II. Product Particulars
Product Name including
strength
Dosage Form
Product Licence No. (if any)
Batch No.
Pack Size
Expiry Date
Manufacturer
Country of
Manufacture
Active Ingredient(s) and
Strength
Type of
product e.g.
medicinal
product,
cosmetic
Example of Defective Products
Notification Form
III. Product Defect Particulars
INFORMATION ON PRODUCT DEFECTS
1
Date of occurrence of defect
2
Nature and cause of defect
3
Number of occurrence of similar defects
4
Results of tests or investigations on suspected
products or other products
5
Assessment of risk to user
6
Proposed action by company including recall
classification and level
7
Other relevant details
Example of Defective Products
Notification Form
IV. Import / Manufacture and Sales Particulars
INFORMATION ON IMPORT / MANUFACTURE / SALE
1
Date and quantity imported or manufactured (for locally
manufactured product)
2
Date and quantity sold or supplied
3
Date and quantity remaining in the warehouse
4
Date and quantity exported and to which country
5
Names and addresses of purchasers of product
*6
(Quantity recalled from purchasers)
Signature
Name of person making report
Date
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