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Guidelines On Recall Rapid Alert System For Medicinal Products 1
Guidelines On Recall Rapid Alert System For Medicinal Products 1
Guideline
General Administration of Market Control
TABLE OF CONTENTS
≠ Content Page
1 Introduction 3
2 Background 3
3 Scope 4
4 Definitions 4
5 Recall Action Classification 7
6 Levels of Recall 7
7 Phases of Recall 8
8 Initiation of Recall 8
8.1 Voluntary Recall 8
8.2 Statutory Recall 10
9 Rapid Alert System 13
10 Implementation of recall 16
10.1 Stepwise Recall Procedure 15
11 Review Phase 18
11.1 Follow-up by the Drug Authority 18
11.2 Follow-up by product licensee 19
12 Appeals 21
13 Disposal 21
14 Procedures for safe disposal 23
15 Disposal Methods 26
Recommended disposal methods according to the dosage 28
16
form and product nature.
17 References 30
Guideline
General Administration of Market Control
1. Introduction
A recall is an action taken to withdraw/remove a drug from distribution or use
including corrective actions for which deficiencies in quality, efficacy or safety have
been reported. Quality-related defective products include substandard,
adulterated or counterfeit medicinal products. Recalls regarding safety and efficacy
include serious adverse reactions and death. The recalls also include medicinal
products prohibited under the Pharmacy Profession Law, as well as products whose
licenses have been suspended / revoked. The recall applies to all pharmaceuticals,
including medicines, biological preparations, cosmetics, and medical supplies.
The rapid alert system is the actions taken in the event of warnings, the urgency
and seriousness of which does not allow any delay in the alert. An assessment
should be made of the severity of the defect and its potential to cause harm to the
patient.
2. Background
According to the law 151 for year 2019 law establishing the Egyptian drug authority
EDA’s objective is to regulate, implement and supervise the quality, efficacy, and
safety of medical products. EDA regulate and supervise the production and
circulation of medical products and devices and raw materials stipulated under this
law, and verify its quality, efficacy, and safety within and outside the republic in the
context of regulating Egyptian products and its representation aboard. EDA Set the
rules and procedures that regulate the processes of import, export, registration,
pricing, circulation, supervision and inspection of medical products and devices
subject to this law and raw materials used in its manufacture, through coordination
with relevant entities and in accordance with international standards.
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3. Scope
This guideline applies to all reports of defective product quality and all safety and
efficacy incidents reported and received for all medications including vaccines and
biologics. This guideline is followed by licensees (manufacturers, importers, agents,
distributors, retailers) and recall can be voluntary or statutory. This guideline can
be applied by other agencies in the event that urgent action is needed to protect
public health or animal health. This guideline will assist in the adoption of the
stepwise actions to be followed in the recall strategy and also help in assessing
recall at each level and compliance with the time frame.
This guideline is mainly applied to the distributed and marketed batches and in case
of the non-conformity of batches that have not been marketed no need for the
issuing of recall.
4. Definitions
Recall: Removal of marketed products for reasons of lack of quality, safety, or
efficacy, including labeling that is against the law.
Batch (es) recall: The process of removing the selected lot(s) from a product that
is found to be defective and poses health risks to consumers if left in the market.
Batch: A specific amount of material produced in a process or series of processes
that is expected to be homogeneous within certain limits.
Customer: Any person, institution or entity that purchases / receives goods from
the company for storage, distribution and sale.
Substandard medical products: also called ‘out of specification’ refer to
authorized medical products that fail to meet either their quality standards, or
their specifications or both.
Falsified medical products: are products that deliberately or fraudulently
misrepresent their identity, composition or source.
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Distributor level:
All levels of distribution between manufacturer and retailer.
All invocations must be executed from
Class I to distributor, retail and consumer levels. In such cases, public advertising
should be done using media, electronic, newspapers, television, and radio etc.,
In addition to obligating the distribution companies to print the recalled item
on their sales invoices.
Class II to distributor and retail levels.
Class III to distributor levels.
7. Phases of Recall
8. Initiation of recall
Any batch of the product that does not meet the specified quality standards must
be withdrawn from the market. The recall can be of two types: Voluntary recall
and statutory recall.
8.1 Voluntary recall
The manufacturer or importer of a medicinal product shall provide the Authority
with request for recall including the following: -
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(a) product name and generic name, dosage form, strength, batch or lot number,
pack size, the name and address of the manufacturer, manufacturing date and
expiry date of the recalled product;
(b) The reason for the recall, the nature of the defectiveness or possible
defectiveness, the date on and circumstances under which the defects or possible
defects were discovered;
(c) The distribution list of the product batch(es) to be recalled containing :
1. Quantities produced or imported
2. Date on which distribution of the product began
3. List of customers to whom product was distributed with the dates of
distribution for each.
(d) The manufacturer or importer of a medicinal product should provide the EDA
with the plan of recall and the timeframe for the recall that is proportional to the
class of recall
(e) The manufacturer or importer of a medicinal product shall submit to the EDA an
investigation report detailing causes of the defect and corrective and preventive
actions undertaken.
EDA will publish the voluntary recall on the website to notify the public after the
voluntary recall request risk assessment.
The manufacturer or importer of a medicinal product shall submit to the EDA a
weekly progress report of recall and the final report after completion of a recall
which includes reconciliation between delivered and recovered quantities of the
product
In case of the manufacturer or importer non-compliance with the plan of recall EDA
will mandate statutory recall and regulatory decision will be taken if needed.
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Further professional assessment of the risk from the product should involve
discussion with the manufacturer or importer and include consideration of:
Any other reports which may be related;
The distribution of the batch (e.g., restricted to known hospitals, widespread
through wholesalers).
Date of first distribution and last distribution.
any remaining stock with the manufacturer or importer.
Probability that other batches are affected in the same way, and their
distribution.
11 Guidelines on recall and rapid alert system for medicinal products
Guideline
General Administration of Market Control
B. On-site inspection
On routine investigation or upon complaint unusual observation has been detected
and thus a recall action is taken into consideration, some points should be stated in
the onsite inspection to help in taking the decision of recall action.
The storage condition should be mentioned to exclude incorrect storage as the
cause of the suspected defect.
Visual inspection is a must and identify if the defect is visible and a full description
of the defect should be described.
It should be stated was the defect identified in a new previously unopened container
or had the container previously been used to exclude user errors such as product
mix-ups and so other unopened containers of the same batch available could be
checked.
If the product is used with a medical device because in some cases the device could
be the cause of the incident
Authority should contact the manufacturer or importer for providing an original
pack for the suspected product to make a comparison between the original and
suspected pack
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C. Previous history.
Previous report of the manufacturing or importing site should be made included and
any comment on general GMP compliance and what related products manufactured
or imported.
On-site inspection may be required to assess batch records of the product
concerned, plant records and records of other batches or products which could also
be affected.
Samples may be taken of the batch concerned, related batches and related starting
materials. When considering taking material from the company’s retained samples,
consideration must be given to the quantity available and all tests which may be
required for further investigations.
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Alert notification can be in multiple forms including press releases, telephone calls,
telegrams, telefaxes, mailgrams, or first-class letters.
Alert notification should be brief and to the point; clearly identify the product(s)
such as the product name, size, brand name, serial numbers(s), potency, dosage,
type, model, and batch number
Alert notification should be sent in the most expeditious manner and
commensurate with the hazard of the product being recalled, and, where
appropriate, sent with proof of receipt (e.g., by certified mail).
The licensee/representative of licensee where the product is marketed shall inform
the concerned regulatory authority where the product batch (es) in question was
distributed immediately after the decision of recall has been taken. Further actions
on recall will be undertaken according to class of recall.
Class II defects could cause illness or mistreatment, but are not Class I. A rapid alert
notification should be sent to all contacts of the rapid alert notification list as it
might be difficult to know where a batch has been distributed. If the product
distribution is known, the notification should be only sent to the contacts
concerned. Whenever feasible, transmission of a Class II rapid alert should be
transmitted within 72 hours.
Class III defects May not pose a significant hazard to health, but notification of the
entire stakeholders should be done within 5 days of the recall letter issuance.
For the falsified product that an alert notice letter or public awareness letter has
been issued a rapid alert notification should be sent to all contacts of the rapid alert
notification list within 24 hours, with a maximum of 72 hours of the issuance.
The contact list for rapid alert notifications shall be used for the transmission of
notification falling in the scope of this procedure and the GMP non-compliance
procedure; these messages should clearly identify the subject and whether they are
for information or action.
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The Product/Batch withdrawal notice sent by the company that owns the product,
the agent for the recalled product, or the responsible head of quality to the
distributor.
After completing these steps, the company that owns the product must provide the
Authority with copies of the notice of product withdrawal explaining the seriousness
of the defect and warning of the reservation of quantities at the distributors and the
withdrawal of the product from the market for each of the distributors indicated in
the distribution statement.
The Distributor shall immediately check the distribution history to identify the
customers and warehouses in which the respective product/runs have been
distributed and send copies of the recall notice to them for further necessary action.
The head of the main store or the head of the sales sector must ensure that the
circulation of the product has been stopped by reviewing the register and at the
same time keeping the available stock.
All branches must send Return Notes with merchandise (if any) to the main store.
All returned stocks must be sent to storage warehouses.
The head of the main store or the head of the sales sector ensure that he sends a
periodic report to the owner of the product or the agent for the product with the
stock available to them and the returns received from the branches.
Head of Main Store or Head of Sales segment should reconcile the stocks of recalled
materials against the total quantity of materials received and fill in “Product
Summary Report / Batch Recall”.
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The copy is sent to the owner of the product or the agent for the product with the
stock they have, and the returns received from the branches for review, taking the
necessary action and preparing for receiving the recalled quantities. The copy is sent
to the competent department of the Egyptian Drug Authority based on the nature
of the recalled product in the quantities to be returned to the companies that own
the product or the agent of the product, the receipt of the owner of the product or
the agent of the returns is monitored.
The recall of the product / lot depending on the recall category must be completed
within the specified time.
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2- Likewise, the recalled product or batch is specific to the local market or hospitals
3- Product consumption rate
4- Quantities in the possession of the owner of the product or agent and in
distribution companies and warehouses, as well as the quantities that were
distributed to pharmacies when the recall publication was issued Summoning class
and summoning level.
A date must be set for the destruction of all the quantities recalled by the owner
of the product or the importer, no later than three months from the date of
issuance of the recall letter or the voluntary recall request, unless a justification is
submitted to the authority and been approved.
11.2 Follow-up procedures for the returned products by the owner of the
product
11.2.1 In case of class II
The follow-up procedure consists of checking the effectiveness of the recall,
investigating the cause of the recall and remedial actions taken to prevent
recurrence of the defect.
The Licensee / Licensee's Representative / Head of Quality Assurance shall
monitor the recall of the product / lot to determine whether the recall is
proceeding satisfactorily.
The stock of returned products must be placed under 'quarantine' and stored
separately under lock and key in a secure area until a further decision is made.
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Where required, the Head of Quality Assurance at the manufacturing site must
perform a physical examination of the recalled merchandise and collect samples of
the returned merchandise for investigation to determine the root cause of a product
quality defect.
Investigation of recovered lot(s) shall be conducted in accordance with Licensee’s
SOP, “Investigation of Non-Conformity” to identify the root cause of failure and
initiate corrective and preventive actions Impact assessment shall be conducted on
other runs of the product concerned and extended to runs of other product(s),
where applicable.
If the reason for recall proves to be a quality issue associated with any of the raw
materials used, then traceability of that material in all products/runs must be
determined through records to identify the batches/products in which the specified
materials were used.
11.2.2 In the case of first class I recall.
Monitor relevant data, i.e., material, plant and lot number in each of them
Determine traceability of raw materials in different formulations and their functions.
List all raw materials with batch numbers and quantities used in those batches.
List all products with batch numbers and related quantities used in those batches.
Calculate the total quantity by adding up the individual quantities used in different
products/batches.
Monitor the movement of materials to get a complete stock overview for that
particular material in the factory and extract information about the total quantity
received and the stock quantity.
The balance, if any, should be checked against the actual physical stock available. A
plan must be made to make a random drawing based on this data to verify the
effectiveness and safety of products or processes.
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The decision to withdraw any affected batches, if necessary, should be made after
evaluating the quality of the product.
Based on the results of the investigation, the Head of Quality Assurance / authorized
representative shall instruct the distributor / marketing company in order to
appropriately dispose of the batch(s) of returned merchandise in accordance with
the regulations.
12. Appeals:
the licensee or manufacturers has the right to submit technical appeal directly to
the head of CA of operation accompanied with all technical justifications within
fourteen days of the recall issuance.
these appeals then directed to the relevant decision to investigate and prepare a
detailed report about the issue in question, accompanied with all related
documents to be viewed by the head of CA of operation for final decision.
Unsatisfied applicants may only resort to Grievance committee, all other appeals
shall be deemed as previously resolved, except for those admitted accompanied
by new technical documents.
Grievance shall be submitted not later than sixty days from the date of the recall
issuance, which will be submitted to the Grievance committee.
a ruling on the grievance shall be rendered within sixty days from the grievance
submission.
13. Disposal
Recalled medical product should be destructed not more than three months of
recall letter issuance unless request from the product licensee is submitted to the
EDA to postpone the disposal for instance in case of appeals and should be
approved by EDA, the destruction of the SF products is mandatory to prevent the
reentrance of these products to the supply chain and thus a unit related to the
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General Administration of Market Control
Market control administration has been developed for the recall follow-up and
disposal of all unwanted medical products.
13.1 The following procedures will be applied on the safe disposal of SF products
as well as:
a-Batches for which non-conformity reports have been issued by EDA and the whole
batch is sealed in the factory and the company wants to destruct them upon its own
request.
b-Batches for which non-conformity reports have been issued internally by the
company and the company wants to destruct them upon its own request.
c-Defected batches after a detailed report carried out by the inspector to find out
the cause and make sure of it.
d-Batches that the technical committee of the EDA issued a decision of disposal
e-Batches that the supreme inspection Committee issued a decision of disposal
f-SF medical products that the competent judicial authorities issued a decision of
disposal
g-Batches for which a decision of disposal has been issued by international
organizations warnings (WHO - EMA- ...)
h-Pilot batches, clinical trial and R&D batches.
The best environmental choice for Medical Product disposal is high temperature
incineration with adequate flue gas cleanup. However, this is not the only method
that can be used to achieve adequate disposal.
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14.2 Decision
The approval and sanctioning of disposal of pharmaceuticals is done after revising
all these documents within 5 working days and respond will be sent to the service
requester email or informing the contact person stating the case of the request as
follows :
1- incase all documents submitted meets the EDA criteria the service requester
will be informed to decide the date of disposal of the products within 14 days
of the informing email otherwise the request will be cancelled
2- 2- In case of missing documents the service requester will be informed by all
the documents needed to be submitted within 5 working days otherwise the
request will be cancelled and upon submission these documents will be
revised within 2 working days for final decision and if these documents meets
the EDA criteria the service requester will be informed to decide the date of
disposal of the products within 14 days of the informing email otherwise the
request will be cancelled
3- In case of needed reports from other administration for instance in pilot
batch disposal the service requester will be informed with the case, the
relevant administration will be contacted to submit the report needed within
5 working days to inform the service requester.
4- In case of the request refusal a full details of the reason of refusal will be sent
to the service requester and another request can be submitted after
corrective actions is done
14.3 Planning
Planning, in terms of human resources, professional time, space, equipment,
material and available disposal options will be required. This is essential before
practical steps can be taken to start disposal. To obtain a rough estimate of the
volume of materials to be sorted, it is recommended that measurements are made
using a tape measure, and conversion from volume of material to weight is made
using a density figure of 0.2 metric tons/cubic meter, which Is mandatory to be
submitted by the request provider
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14.5 Sorting
The objective of sorting is to separate the pharmaceuticals into separate categories
for which different disposal methods are required. EDA auditors shall go to the
warehouse where the products are kept to supervise and follow up the work of the
committee formed by the service requester to carry out the disposal process to
ensure the type and quantity of products to be destructed and the expiration date
compared with the list approved to be destructed and then all these inventory items
sealed whether in a separate warehouse or in the trucks for transportation by the
auditor’s seal.
14.6 Disposal
The EDA auditors shall go the day after to the execution site to supervise the disposal
process and ensure the safety of the seals and to follow up on the disposal process
of all the products that have been released. The disposal shall be carried out in
accordance with method and place mentioned in the notification letter
In the case that the EDA Auditors observed any lack of safety of the seals or the
existence of any change in the type or quantity of products to be destructed or
change the method of disposal, auditor
25 Guidelines on recall and rapid alert system for medicinal products
Guideline
General Administration of Market Control
will stop disposal process and write report and justification from the applicant should
be admitted within 24 hours.
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safe disposal of any medical product due to pollution, with the risk of drinking water
contamination in the worst cases and also subjecting to scavenging.
B) Engineered landfill Such a landfill has some features to protect from loss of
chemicals into the aquifer. Direct deposit of pharmaceuticals is second best to
discharging immobilized pharmaceutical waste into such a landfill.
C) Highly engineered sanitary landfill
An appropriate landfill consists of an evacuated pit isolated from watercourses.
15.2 Waste immobilization: encapsulation
It involves immobilizing the pharmaceuticals in a solid block within a plastic or steel
drum.
15.3 Waste immobilization: inertization
It is a variant of encapsulation which transform the pharmaceutical product into
homogenous paste, The paste is then transported in the liquid state by concrete
mixer truck to a landfill and decanted into the normal urban waste.
15.4 Sewer
Some liquid pharmaceuticals, e.g. syrups and intravenous (IV) fluids, can be diluted
with water and flushed into the sewers in small quantities over a period of time
without serious public health or environmental affect.
15.5 Burning in open containers
This method is not approved by EDA , as toxic pollutants may be released into the
air.
15.6 Medium temperature incineration
Two–chamber incinerator that operates at the minimum temperature of 850°C,
with a combustion retention time of at least two seconds in the second chamber.
15.7 High temperature incineration
Furnaces that operate at temperatures well in excess of 850°C, have long
combustion retention times and disperse exhaust gases via tall chimneys, often to
high altitudes.
These furnaces existing in industrial plants Industries which use high temperature
technology, such as cement kilns13, coal fired thermal power stations or foundries.
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16.Recommended disposal methods according to the dosage form and product nature.
16.1 Antineoplastic
Antineoplastic should be segregated from other pharmaceuticals and kept
separately in clearly marked containers.
First option: High temperature incineration
Second option: Waste immobilization: encapsulation
Antineoplastic drugs/waste should never be disposed of in a landfill or disposed in
sewer or watercourses or even use medium temperature incineration
16.2 Anti-infective drugs
first option: High temperature incineration
Second option: Waste immobilization: encapsulation or Inertization
Liquid anti-infective drugs may be diluted in water, left for two weeks and
disposed to the sewer.
Anti-infective drugs should not be discarded in an untreated form.
16.3 Disinfectants
In general disinfectants do not have an expiry date. If possible, disinfectants should
be used, for example for toilet cleaning in hospitals. Some disinfectants with strong
bactericidal and antiviral activity, such as Lysol (50% cresylic acid), may have an
expiry date. If this date has passed, the material can still be used for general
disinfection purposes at an appropriate dilution decided by a pharmacist, or
disposed of in a chemical waste disposal facility or a cement kiln.
Large quantities of disinfectants must not be flushed into the sewer, as they may
kill the bacteria in a sewage works and so stop the biological treatment of the
sewage. Similarly, large quantities should not be put into watercourses since the
disinfectants will damage aquatic life. Small quantities of diluted disinfectant may
be disposed of by discharge to a sewer.
16.4 Pesticides
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they are not disposed and should be shipped out of the country.
16.5 Solids, semi-solids and powders
Small quantities of solid and semi-solid pharmaceuticals, can be disposed of directly
in an Engineered landfill with large volumes of municipal solid waste, if no other
suitable method is available.
Large quantities of solid and semi-solid pharmaceuticals are best destroyed by high
temperature incineration. Medium temperature incineration is however widely
practiced for solid form pharmaceuticals, provided that the pharmaceuticals are
“diluted” in large quantities of municipal waste. The use of the encapsulation
method represents an acceptable, but not always feasible, method of disposal for
large quantities of pharmaceuticals.
16.6 liquid pharmaceuticals (except controlled drugs, antineoplastic or anti-
infective drugs)
They may be diluted and flushed into a sewer. . If there are no sewers or there is no
functioning sewage treatment plant, liquid pharmaceuticals can be first diluted with
large volumes of water and poured into large watercourses, providing they are
immediately dispersed and diluted by the flowing river water. Liquid
pharmaceutical waste may be disposed of using the cement encapsulation
procedure, high temperature incineration or in cement kilns.
16.7 Ampoules
These can be crushed on a hard impermeable surface (e.g., concrete) or in a metal
drum or bucket using a stout block of wood or a hammer. The crushed glass should
be swept up, placed in a container suitable for sharp objects, sealed and disposed
of in a landfill. The liquids released from the ampoules should be diluted and
disposed of as described above.
Ampoules should not be burnt or incinerated as they will explode, possibly causing
injury to operators and damage to the furnace or incinerator. Melted glass will also
clog up the grate of a furnace or incinerator if the operating temperature is above
the melting point of glass.
NB: Ampoules of antineoplastic or anti-infective drugs must not be crushed and the
liquid discharged to sewers. They should be treated using the encapsulation or
inertization disposal methods described
29 Guidelines on recall and rapid alert system for medicinal products
Guideline
General Administration of Market Control
above.