Drug Recall Procedure in ASEAN Countries

 

Sara Jabeen¹, Sridhar S¹, Balamuralidhara V²

¹Regulatory Affairs Group, JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagara, Mysore – 570015, Karnataka, India

²Assistant Professor, Regulatory Affairs Group, Department of Pharmaceutics, JSS College of Pharmacy,

JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagara, Mysore – 570015,

Karnataka, India

 

ABSTRACT:

Once the product is successfully placed in the market which after a period of time was found to pose risk to human health is required to be recalled from the market to protect the health of the public, where in, the recall of the product consist of well-established written procedures and systems to record, access, investigate and review the potential quality defects to safe guard the public health from the low quality or damaged products. The recall of the product should be effective and prompt for medicinal products and investigational medicinal product from the distribution chain and necessitate the application of quality risk principles for investigation and assessment of the quality defects. The main objective in the process of product recall from the market, regulatory authorities plays an important role in guiding manufacturers by benchmarking the standard procedure for the efficient recall of the quality defect products from the chain, the procedures & classification under which the recall falls and its timeline for the efficient recall of the product is  also guided by the authority to protect the health of the public and animals in case of the veterinary products in ASEAN member countries where different recall procedures are opted. The present study highlights the comparison of recall procedure among Malaysia, Philippine, Thailand, Singapore, Vietnam which falls under ASEAN countries.

 

 

INTRODUCTION:

A drug recall removes a prescription or over-the-counter drug from the market. Drug recalls in the United States are made by the FDA or the creators of the drug when certain criteria are met. When a drug recall is made, the drug is removed from the market and potential legal action can be taken depending on the severity of the drug recall.

 

 

 

 

 

 

Class I ·   Most severe ·   Adverse health effects or death

Class II ·   Induce temporary and/or medically reversible health effects

Class III ·   Adverse health effects are not likely to occur when consuming the drug or being exposed to it.

Fig. 1: Drug recalls are classified in the US by the FDA in three different categories

 

The recall procedure depends on Drug type

Notification of defective product is made to regulatory authority and waits for response

Processing and tracking

Compliance and reporting – conduct an effective cheek

Fig. 2: Hierarchy of Recall Procedure

 

 

Reasons for Drug Recall:

1. Hazardous to Health:

Although clinical trials are often conducted, it is difficult to tell if there are long-term side effects of medicines from lab testing for short periods of time. Drugs can cause a higher chance of stroke, heart problems, and death in some patients, making them unsafe to use and requiring a recall.

 

2. Poorly packed and mislabelled:

Sometimes the instructions on a medication label are unclear or misleading, which can lead to an overdose, under-dose or other adverse effects. If the authority receives reports that patients are taking a drug incorrectly due to insufficient instructions, it will recall the medication.

 

3. Contamination:

If proper precautions are not taken during manufacturing, it is possible that there can be chemical contamination. Facilities that manufacture multiple drugs need to be particularly careful that their production is sterile and free of any drug or chemical residue that can find its way into the drug.

 

4. Mismatched Drug:

Though rare, the medication inside a drug package sometimes is not the correct medication. Before you take a new drug, find out what the pill looks like, and verify that the medication you received looks the same.

 

5. Interacts with specific drugs and food

In some cases, consumers of a specific pharmaceutical are on a unique regiment of drugs that are calculated to be safe. When a drug is introduced to the market, it is possible that it has not been tested with their combination of drugs, leading it to interact and cause adverse effects. The same can happen with foods or drinks, with alcohol often presenting complications with medicines.

 

DISCUSSION:

Table 1: country profile of 5 member states of ASEAN country

PARAMETERS	MALAYSIA	PHILLIPINES	SINGAPORE	THAILAND	VIETNAM
Country name	Federation of Malaysia	Republic of the Philippines	Republic of Singapore	Kingdom of Thailand	Socialist Republic of Vietnam
Capital	Kuala Lumpur	Manila	Singapore	Bangkok	Hanoi
Largest city	Kuala Lumpur	Quezon City	Bedok	Bangkok	Ho Chi Minh City
Population	31 million	104 million	5.3 million	69 million	92 million
Area	329,847 sq km (127, 355 sq miles)	300,000 sq km (115, 831 sq miles)	660 sq km (255 sq miles)	513,115 sq km (198,115 sq miles)	329, 247 sq km (127, 123 sq miles)
Major language	Malay (official), English, Chinese dialects, Tamil, Telugu, Malayalam	Filipino, English (both official)	English, Malay, Mandarin, Tamil	Thai	Vietnamese
Major religions	Islam, Buddhism, Taoism, Hinduism, Christianity, Sikhism	Christianity	Taoism, Buddhism, Islam, Christianity, Hinduism	Buddhism	Buddhism
Life expectancy	73 years (men), 78 years (women)	66 years (men), 73 years (women)	79 years (men), 84 years (women)	71 years (men), 79 years (women)	73 years (men), 81 years (women)
Currency	Ringgit (1Ringgit = 18 INR)	Philippine peso (1 Philippine peso = 1.36 INR)	Singapore dollar (1 Singapore dollar = 53.35 INR)	baht (1 bhat = 2.23 INR)	dong (1 dong = 0.0032 INR)
Government	Federal parliamentary elective constitutional monarchy	Unitary presidential constitutional republic	Unitary dominant-party parliamentary republic	Unitary parliamentary constitutional monarchy	Unitary Marxist-Leninist one-party socialist republic
Regulatory authority	National Pharmaceutical Regulatory Agency - NPRA	Food and Drug Administration Philippines	Health Sciences Authority (HSA)	Thai Food and Drug Administration (TFDA)	Drug Administration of Vietnam (DAV)

 

Malaysia:

·       Malaysia boasts one of south-east Asia's most vibrant economies.

·       Malaysia is a multi-ethnic, multi-religious federation of 13 states and three federal territories.

·       The majority Muslim ethnic Malay (Table 1: country profile of 5 member states of ASEAN country) are dominant politically.

·       large ethnic Chinese minority holds economic power.

 

Definition:⁽¹⁾

In Malaysia, Product recall is a process taken by the manufacturer, importer and wholesaler to remove or withdraw a particular material and/or product and/or cosmetic from all links of distribution.

 

The removal or withdrawal of product may be due to critical quality defects discovered or serious adverse drug reactions reported which might cause health risks to users of the materials and/or products and/or cosmetics.

 

The Control of Drugs and Cosmetics Regulations 1984 requires every licensed manufacturer, importer and wholesaler to have a procedure (Product Recall Procedure), which sets out in a step-wise manner the various actions to be taken to ensure the prompt recall of defective products. 

 

Decision for recall:

The decision for recall shall be made when there is or may cause potential risk to the user of the materials and/or products and/or cosmetics by reason of faulty production or on medical grounds:

i.      Voluntarily undertaken by the manufacturers and distributors.

ii.    As directed by the Director of Pharmaceutical Services, Ministry of Health.

 

Degree and level of recall:⁽¹⁾

The following criteria are used to classify the degree and level of recall.

A)   Degree of recall

The degree of recall is classified according to the severity of quality defects and adverse reactions of the products 

Degree I Materials and/or products and/or cosmetics with major health risks that might cause serious injuries or death. It should be under an embargo within 24 hours

Degree II Materials and/or products and/or cosmetics with minor health risks or are substandard. It should be under an embargo within 72 hours.

Degree III Materials and/or products and/or cosmetics with other reasons for recall. It should be under an embargo within 30 days or as specified.

 

 

B)   Level of recall⁽²⁾

The level of recall depends on the nature of problem, extent of the material or product or cosmetic’s distribution and degree of hazard involved.

 

 

 

Level A. To all consumers (end users)

Level B. To all points of sales (e.g. Hospitals, Pharmacies, Clinics, Specialists Centres)

Level C. To all sub-distributors (wholesalers)

 

 

Fig. 3: Sources and channels of information to assess recall effectiveness⁽³⁾

 

 

The decision to recall product depends on the degree and level of recall
Director of Pharmaceutical Services, Ministry of Health – specifies degree & level of recall for products
Product recall committee decides decides product recall based on risk
Two persons are appointed for product recall
The parties involved are notified
Product recall Information is circulated
Once the recalled product is back it is sealed and kept separately
Evaluation of recalled product is performed
The final report is forwarded to National Pharmaceutical Control Bureau.

Fig. 4: Stepwise approach to complete recall of a product in Malaysia ⁽⁴⁾

Singapore

·       Singapore is a wealthy city state in south-east Asia. It is described as one of Asia's economic “tigers”.

·       Chinese account for more than 75% of Singapore's multi-racial population (Table1: country profile of 5 member states of ASEAN country)

 

Recall:⁽⁵⁾

“Recall”, in relation to a therapeutic product (TP), means any action taken by its manufacturer, importer, supplier or registrant to remove the TP from the market or to retrieve the TP from any person to whom it has been supplied, because the TP

a).   May be hazardous to health;

b).   May fail to conform to any claim made by its manufacturer or importer relating to its quality, safety or efficacyor

c).   May not meet the requirements of the Health Products Act.

 

Classification of product defects:⁽⁶⁾

(I) Critical defect

A critical defect is deemed as one that can pose a serious threat to the intended users or public health in Singapore. In this guidance, a serious threat means a hazard that occurs in association with the use or administration of a TP and that may lead to the death of, or a serious injury to, any person. 

 

Serious injury refers to an incident that

a)     May result in a person being hospitalised or prolong a person’s existing stay in hospital

b)    May result in a person’s disability or incapacity or

c)     May result in a congenital anomaly or birth defect.

 

(II) Non-critical defect

A non-critical defect is one which does not meet the criteria of “critical defect” but may cause illness or affect the outcome of a person’s medical treatment and/ or significantly affect the quality of a TP.

 

Company duties:⁽⁷⁾

A company may initiate a recall of a therapeutic product (TP) when it presents a risk or even if the defect does not pose a risk to the intended user and/or public health, or for reasons other than product defects (e.g. commercial reasons).

 

Table 2: Outline on company duties and timelines to report defect

Parameters	Report product defects to HSA (Health Science Authority)	Record maintenance	Notify HSA about product recalls
Company duties	Aware of defect, HSA should be reported	Records maintained by All manufacturers, importers and registrants. During inspection produce records to HSA	Plans to recall product notify HSA
Time	·   Critical defects - report within 48 hours*; ·   Non-critical defects – report within 15 calendar days.	Maintain record for at least two year for every defect found in TP	Reason for the recall should be provided no later than 24 hours

 

Classification of recall and recall timelines:⁽⁸⁾

Table 3: Recall classification as Class 1 or Class 2 depending on the potential hazard of the defect.

	Class 1 recall	Class 2 recall
Description	There is a reasonable probability that the use of or exposure to a TP with critical defect which may cause serious adverse health consequences or death.	The use of or exposure to a TP with non-critical defect which may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.
Notification to HSA	Company must notify HAS within 24 hours (1 day) * prior to the start of the intended recall.	Company must notify HAS within 24 hours (1 day) * prior to the start of the intended recall.
Issuance of Dear Purchaser Letter	Company is required to issue a Dear Purchaser Letter within 1 day* of recall commencement, notifying of the recall action and providing the required instructions to purchasers, including immediate cease in sale and supply of the product.	Company is required to issue a Dear Purchaser Letter within 3 days* of recall commencement, notifying of the recall action and providing the required instructions to purchasers.
Recall process	The recall process is recommended to be completed within 1 week, unless otherwise justified. Company should submit the Product Recall Completion Form to update HAS on the completion of recall.	The recall process is recommended to be completed within 3 weeks, unless otherwise justified. Company should submit the Product Recall Completion Form to update HSA on the completion of recall

***Not including Sundays and public holidays.

 

Level of recall:

The level of product recall will depend on the potential hazard of the affected product, extent of distribution and whether other mitigating measures can be taken to address the defect. There are 3 levels of recall:

 

 

 

Philippines:

·       More than 7,000 islands make up the Philippines, but the bulk of its fast-growing population lives on just 11 of them.

·       The Philippines - a Spanish colony(Table 1: country profile of 5 member states of ASEAN country), Spanish influence remain strong especially in terms of language, religion and government.

·       Section 5 (1) of Republic Act No. 9711 mandated the FDA to require all manufacturers, traders, distributors, importers, exporters, & other parties involved to report to the FDA of any incident that a product has caused or contributed to the death, serious illness or serious injury to a consumer, a patient, or any person.

·       Section 5 (k) of the same law empowers the FDA, after due process, to order the ban, recall, and/or withdrawal of any health product found to have caused the death. serious illness or serious injury to a consumer or patient

 

Recall:⁽⁹⁾

Recall is the method of withdrawing or correcting unsafe or hazardous health products from the distribution chain that may present a health hazard to the consumer or user. It is an action taken by establishments involved in the supply chain (e.g., manufacturers, distributors. or retailers) as

(1) part of their responsibility to protect the public health and well-being.

(2) Compliance to the appropriate good practices (e.g., good manufacturing, distribution, or storage practices), and

(3) Compliance to existing standards and regulations.

 

Classification of product recall:⁽¹⁰⁾

Class I Recall Product defects/conditions that are potentially life threatening or could result to severe health risk, health impairment or effects such as permanent damage to health or death.

Class II Recall Product defects/conditions that could cause poisoning or temporary/medically reversible adverse health problem or mistreatment.

Class III Recall Product defects/conditions that may not pose a significant hazard to health, but withdrawal may have been initiated for other reasons.

 

 

Consumer level		Retail level		Wholesale level
risk to patients or consumers is assessed to be unacceptable		risk to patients or consumers is assessed to be moderate to high but recall at consumer level is not deemed necessary		risk to patients or consumers is assessed to be low or where other measures can be taken to mitigate the risk to prevent disruption in supply of critical TPs

 

Fig. 5: Stepwise approach to complete recall of a product in Singapore

 

 

Fig. 6: Stepwise approach to complete recall of a product in Philippines ⁽¹¹⁾

 

Table 4: Details on 3 levels of violation with its timeframe

Levels of violation	What?	Scope and time of recall
Level-1 violation	violation in which a drug is likely to cause serious harms to users’ health or affect user’s life;	The recall shall be completed within 3 days from the date of issuance of a recall decision
Level-2violation	violation in which there is evidence that a drug cannot ensure full treatment effect or is likely to be unsafe to users but not to the extent of causing serious harms to users’ health or affecting users’ life;	The recall shall be completed within 15 days from the date of issuance of a recall decision
Level-3 violation	Violation other than violations prescribed at the Clause which is due to other causes but does not affect treatment effect and users’ safety.	The recall shall be completed within 30 days from the date of issuance of a recall decision

 

 

Vietnam:

·       Vietnam, a one-party Communist state, has one of south-east Asia's fastest-growing economies and has set its sights on becoming a developed nation by 2020.

·       It became a unified country once more in 1975 when the armed forces of the Communist north seized the south. (Table 1: country profile of 5 member states of ASEAN country)

 

 

 

 

Types of recall, levels of violation and time of recall, and disposal of recalled drugs:⁽¹²⁾

1. Types of recall include:

a. Voluntary recall, which is voluntarily effected by a drug registration establishment, drug manufacturer, drug importer or entrusted importer;

b. Compulsory recall, which is effected under a decision of a competent state agency in the cases as prescribed

2. Levels of violation with respect to a drug include:

 

 

 

Fig. 7: Stepwise approach to complete recall of a product in Vietnam⁽¹³⁾

 

Thailand:

·       Thailand is the only country in south-east Asia to have escaped colonial rule.

·       Buddhist religion, the monarchy and the military have helped to shape its society and politics. (Table 1: country profile of 5 member states of ASEAN country)

 

Source of Complaints:⁽¹⁴⁾

Internal complaints: Complaint can be from production, quality control, warehouse, and marketing division

External complaints: complaint can be from customers, doctors, paramedics, clinics, hospitals, pharmacy, drugstores, supermarkets and National Regulatory Authority (NRA).

 

Classification of product recall:⁽¹⁵⁾

Class 1 Recall:

Initiated when the product defect poses a life-threatening situation to users. Some examples of defects that will result in Class 1 recall are contamination with toxic substances and products with major labelling errors. Such recalls shall be accorded with highest urgency and reported to NRAs immediately.

 

Class 2 Recall:

Initiated when the problem or defect is unlikely to cause serious harm to users. Some examples of defects that will result in Class 2 recall include products with minor labelling errors or products which fail to meet product specification or pharmacopoeia standards but are likely to cause minimal hazard to users.

 

Complaint is received

A recall decision is instructed by managing director

The extent and nature of recall is determined by designated person by turning on to regulatory authority and management

recipients of the affected product shall be notified the nature of the recall by telephone. For end-user recall, means of appropriate mass media communication should be considered

recipients of the affected product shall be notified the nature of the recall by telephone. For end-user recall, means of appropriate mass media communication should be considered

National Regulatory Authority and Overseas Regulatory Authorities for which the affected product batch is exported should be notified of the recall

All recalled goods collected from the market shall be clearly identified and stored in the designated secure area while awaiting Management’s decision or National Regulatory Authority’s instruction on their fate

progress of the recall process should be recorded, and a final report issued

Mock recall shall be carried out on a yearly basis to assess the effectiveness recall system put in place

Fig. 8: Stepwise approach to complete recall of a product in Thailand⁽¹⁶⁾

 

CONCLUSION:

The written procedures and the management are responsible for the efficient recall of the product which is not standard there should be the written procedure for the efficient recall of the products from the market before the patient gets effected and the regulatory authority plays an important role by advertising the recall product and the notification to the public by website to safe guard the health of the public and patient& the comparison studies of various ASEAN member countries project the importance of framing recall procedures and its compliance by the manufacturers helps in building up the quality fulfilled product whenever the product poses harmful effect.

 

CONFLICT OF INTEREST:

The authors presenting the paper entitled “Drug Recall Procedure in ASEAN Countries” does not pose conflict of interest.

 

REFERENCES:

1-     Standardsusers.org/Clients/standardsusers/.../dms_product%20safety%20recall.docx

2-     https://www.npra.gov.my/index.php/en/component/content/article/2-uncategorised/640-product-recall-procedures?Itemid=437

3-     http://mystandard.kpdnkk.gov.my/mystandard_portal2014/index.php?r=column/cfive&id=67

4-     https://www.mda.gov.my/mdb/

5-     https://asean.org/storage/2012/10/ASEAN-TMHS-GMP-Training-Chapter-9-Complaints-and-Recalls-FD-00000002.pdf

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7-     https://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Safety_Information_and_Product_Recalls/Overview.html

8-     https://www.hsa.gov.sg/content/dam/HSA/HPRG/Safety_Alerts_Product_Recalls_Enforcement/Guidance%20for%20Industry_Reporting%20of%20therapeutic%20product%20defects%20and%20recall%20of%20TPs_Nov2016_v1revised.pdf

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10-   https://www.doh.gov.ph/product-recall

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12-   http://vbpl.vn/TW/Pages/vbpqen-toanvan.aspx?ItemID=11099

13-   https://dav.gov.vn/upload/attach/8122015_qt_cl_11_03_en_recall_of_defected_vaccine.pdf

14-   https://www.tilleke.com/resources/pharmaceutical-product-recall-new-fda-requirements

15-   http://fscf-ptin.apec.org/docs/events/food-safety-recall-system-development-and-strengthening/Appendix%2027.pdf

16-   https://morulaa.com/thailand-food-and-drug-administration-thai-fda/

 

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Received on 17.05.2019           Modified on 21.06.2019

Accepted on 30.07.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(12): 6041-6048.