A Study on Pharmaceutical Drug Recall

Bansi l. Bhalodiya¹*, Amit Kumar J. Vyas¹, Ajay I. Patel¹,

Ashvin V. Dudhrejiya¹, Ashok B. Patel²

¹Department of Quality Assurance, B.K. Mody Government Pharmacy College, Rajkot, India.

²Government Pharmacy College, Gandhinagar, India.

*Corresponding Author E-mail: bansibhalodiya2@gmail.com

ABSTRACT:

The present study describes the pharmaceutical drug recall in different five countries to evaluate the drug recall that occurred in the last three successive years. The different countries have different regulations for drug recall. Drug product recall is an action taken to withdraw or remove a batch or an entire production run of drug product from distribution or use to return them to manufacturer.it is usually done due to deficiency in quality, safety and efficacy. In the USA, guidelines for drugs product recall are described under 21 CFR Parts 7, 107 and 1270. In Australia, guidelines for drugs product recall are described under section 65F of trade practices act 1974. In Canada, it includes under section 25 of Natural Health Products Regulations (NHPR). In India it includes under para 27 and 28 of schedule M. In South Africa SAHPRA (South African Health Products Regulatory Authority) guidelines are responsible for regulations of drug product recall. Majority of drug recalls occur in the United states due to various reasons. In 2020-2022 total 257 drugs were recalled in Last three years. In Canada and Australia 220 and 25 drugs are recalled respectively. India and South Africa have recalled 2 and 21 drugs respectively. By the observation we can conclude that India and South Africa have a smaller number of recalls. In the USFDA number of drug recalls are decreasing due to following up the laws and regulatory.

KEYWORDS: Drug recall, USFDA, Canada, South Africa, Australia.

1. INTRODUCTION:

Recalling a drug product involves taking it off the market or from distribution when there are issues with its quality, effectiveness, or safety. Adulterated or spurious pharmaceuticals are among the quality-related defective items. Serious adverse reactions and fatalities are among the recalls relating to safety and effectiveness. Drugs that are illegal under the law and products whose product licences have been suspended or revoked are also included in recalls.¹

According to the world health organization's rules for good manufacturing practices, a company must have plans in place in the event that pharmaceutical items need to be recalled or withdrawn.

The majority of nations have added comparable legal provisions, either covering all types of goods or only pharmaceuticals.

Nearly all nations define the recall as a tool for enhancing the quality system and defending public health. While in India, the Drugs and Cosmetics Act 1940 and Rules 1945 defines product recall, complaints, and adverse reactions in Para 27 and 28 of schedule M (Good Manufacturing Practices) to cause serious to minor public health harm. One of the most typical sources of complaints is FORM-483. After any site has been inspected, it is used by the FDA investigator of the office of regulatory affairs to record inspectional results. It is also known as inspectional observation, and the USFDA²also produces establishment inspection reports that help them decide whether or not to take action. The USFDA will send a warning letter if the business or manufacturer doesn't reply to the observations within 15 days³

2. USFDA:

2.1 INTRODUCTION:

Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services. In the USA, guidelines for drug product recall are described under 21 CFR Parts 7, 107 and 1270.⁴

The US-FDA is responsible for protecting and promoting public health through the control and supervision food and drug products in pursuant to the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301) and other laws are responsible for the quality drugs available to be public.⁵

When Food and Drug Administration (FDA) found a violation of the laws, it issues a recall order by which a firm remove or correct the market product.⁶

2.2 CLASSIFICATION OF RECALL:

The FDA drug recall and other actions have been classified as the following five categories:⁷

· Class I recall: Includes a health hazard situation where there is reasonable possibility that the use of the product will lead to serious, adverse health consequences or death.

· Class II recall: Includes a potential health hazard situation where there is a remote possibility of adverse health consequences from the use of the drug product.

· Class III recall: Includes a situation where the use of the drug product is not likely to cause adverse health outcomes.

Table 1: List of Drugs Has Been Recalled Recently

Date (MM/DD/YY)	Brand name	Product description	Reason of recall	Company
01/12/2022	Viona	Metformin Hydrochloride Extended-Release Tablets	N-Nitrosodimethylamine (NDMA) Impurity^[8]	Viona Pharmaceuticals, Inc.
03/22/2022	Accuretic, Greenstone Brand	Accuretic™ (quinapril HCl/hydrochlorothiazide); quinapril and hydrochlorothiazide; and quinapril HCl/hydrochlorothiazide	Presence of a nitrosamine, N-nitroso-quinapril	Pfizer
03/07/2022	Fresenius Kabi USA	Sodium Acetate Injection, USP, 400 mEq/100 mL (4 mEq/mL), 100 mL fill in a 100 mL vial	Due to the presence of particulate matter found in reserve and/or stability sample vials.	Fresenius Kabi, USA
05/23/2022	Teva	Anagrelide Capsules	Dissolution Test Failure	Teva pharmaceuticals USA.
04/22/2022	Pfizer	Accupril (Quinapril HCl) tablets 10mg, 20mg, 40 mg	Due to N-Nitroso-Quinapril Content	Pfizer pharmaceuticals.
07/13/2022	Hospira	Propofol Injection Emulsion, USP	Potential presence of visible particulate	Hospira Inc, A Pfizer Company
08/04/2022	Major	Milk of Magnesia, Magnesium Hydroxide/Aluminium Hydroxide/Simethicone Oral Suspension	Microbial contamination	Plastikon Healthcare, LLC

2.3 Observation of Recall in the United States:

Figure 1: Number of drug recalls happened in the last three years in the United States.

3. AUSTRALIA.⁹:

3.1 INTRODUCTION:

A recall action is a set of market actions that are undertaken via the Uniform Recall Procedure for Therapeutic Goods (URPTG) to resolve a problem with a therapeutic good already supplied in the Australian market for which there are issues, deficiencies or defects in relation to the safety, quality¹⁰, efficacy, performance or presentation of the therapeutic good.

Recall actions vary on a case-by-case basis depending on the deficiency, issue or defect associated with the therapeutic good and the risk this poses to public health and safety.

3.2 RECALL CLASSIFICATION:

To assist in the identification of the nature of a recall action, they are classified into one of the following classes based on the potential risk the deficiency, issue or defect poses to patients/consumers:

● Class I - Most serious safety-related - recall action occurs when there is a reasonable probability that the use of, or exposure to, the deficient therapeutic good(s) will cause serious, permanent or long-term adverse health consequences or death.

● Class II - Urgent safety-related - recall action occurs when the use of, or exposure to, the deficient therapeutic good(s) may cause temporary or medically reversible adverse health consequences, or where the probability of serious adverse health consequences is remote.

● Class III - Lowest risk - recall action occurs when the use of, or exposure to, the deficient therapeutic good(s) is not likely to cause adverse health consequences and they are therefore not safety related.

Table 2: Examples of some recent drug recall

Date (YY/MM/DD)	Product description	Reason of recall
2020/02/14	Palexia SR 100 mg tapentadol tablet	Labelling fault
2021/06/03	Ospolot (sulthiame) tab 200 mg	Child resistant caps may not function correctly
2022/04/22	Kynd stress relief tablet	Allergic reaction.
2022/07/06	Lucas papaw ointment	Microbial contamination.

FIGURE 2: Number of drug recalls happened in the last three years in Australia¹¹.

4. CANADA.¹²:

4.1 INTRODUCTION:

Recall – A responsible party's removal from further sale or use, or correction, of a distributed product that presents a risk to the health of consumers or violates the Act or the Regulations. This section tells you how to complete all stages of a drug or natural health product recall¹³.Unless stated otherwise, the following guidance is for the responsible party initiating the recall. This guide is for anyone working with drugs or natural health products. It will help facilitate understanding and compliance with sections of the Food and Drugs Act (the Act), the Food and Drug Regulations (FDR) and Natural Health Products Regulations (NHPR) that relate to recalls. When a product has a potential health risk or contravenes the legislation Health Canada administers, you may need to initiate a recall for the product.

4.2 RISK ASSESSMENT AND CLASSIFICATION OF RECALL:

Health risk assessment Before deciding to conduct a recall, you should:

● Evaluate the risk associated with a product that presents a risk to the health of Canadians assess the risk over the product's shelf life (i.e., both now and at the expiry date)

● Ensure your assessment accounts for any reported adverse reactions and intended use population

● Assess whether there are contraventions of the legislation Health Canada¹⁴administers.

● Use the results of your health risk assessment to assign a health risk classification (Type I, II or III) for the recall, as follows:

● Type I: Assign this type to a situation in which there is a reasonable probability that the use of (or exposure to) a recalled product will cause serious adverse health consequences or death.

● Type II: Assign this type to a situation where the use of, or exposure to, a recalled product may cause temporary adverse health consequences, or where the probability of serious adverse health consequences is remote.

● Type III: Assign this type to a situation where the use of (or exposure to) a recalled product is not likely to cause any adverse health consequences.

Table 3: List of Drug Has Been Recalled Recently

Date (YY/MM/DD)	Description	Type	Reason of recall	Company
2020/12/14	Pregabalin capsule	Type 2	Concentration of drug is outside acceptable limit	Pfizer
2020/02/26	Metformin HCL 500 and 825 mg	Type 1	Presence of nitroso dimethylamine (NDMA) Impurities.	Sun pharma Inc. Canada
2021/04/06	Varenicline tartrate 0.5 mg and 1 mg.	Type 2	N- nitroso varenicline Impurities.	Teva Pharmaceuticals, Canada
2021//05/21	Valsartan 80 mg,160 mg and 320 mg.	Type 1	5-(4-azidomethyl) -(1,1- biphenyl-2-yl-)- 1H- tetrazole.	Sanis health Inc, Canada
2022/01/06	Amitriptyline 10 mg	Type 1	Presence of nitroso dimethylamine (NDMA) Impurities.	Apotex Inc, Canada
2022/01/31	Dasatinib 140 mg	Type 3	Dissolution is out of specification	Dr. Reddy labs, Canada
2022/02/03	Itraconazole solution	Type 3	Assay is out of specification	Odan laboratories.

4.3 Observation of Recall in Canada. (2020-2022):

FIGURE 3: Number of different classes of drug recall happened in the last three years in Canada.

5. INDIA.^15-19

5.1 INTRODUCTION:

Recall is an action taken to withdraw/remove the drugs from distribution or use including corrective action for which deficiencies are reported in quality, efficacy or safety. The defective products related to quality include Not of Standard Quality, Adulterated or Spurious drugs. Safety and efficacy related recalls include serious adverse reactions and death. Recalls also include drugs prohibited under the Provisions of Drugs & Cosmetics²⁰Act and also those products for which product licenses are suspended/cancelled.

5.2 RECALL CLASSIFICATION:

Class I is a situation in which there is a reasonable probability that the use of, or exposure to, a defective product will cause serious adverse health consequences or death and as well as be banned under 26A of Drugs and Cosmetics Act 1940.

Class II is a situation in which the use of, or exposure to, a defective product may cause temporary adverse health consequences or where the probability of serious adverse health consequences is remote.

Class III is a situation in which the use of, or exposure to, a defective product is not likely to cause any adverse health consequences.

5.3 RECALL PROCEDURES:

Any batch of a product not meeting the defined quality standards has to be recalled from the market. Recall can be of two types; Voluntary Recall and Statutory Recall.

Voluntary Recall: Voluntary recall can be triggered by any incident that affects the quality, safety and efficacy of the batch/product.

Statutory Recall: Statutory recall can be triggered in response to the direction or mandate by the Drug Regulatory Authorities²¹(Central/State) in one or more of the situations as follows:

1. To recall the drug product/batch, considered to be in violation of the laws, it administers such as not of standard quality etc.

2. To recall the banned drugs.

3. Labelling and / or Promotional materials, that are considered to be in violation of law

4. Product, violation Rule 106 (Diseases under Schedule J).

5.4 LEVELS OF RECALL:

There are three levels of recall such as consumer/user, retail and wholesale.

1. Consumer or User Level: which may vary with product, including any intermediate wholesale or retail level. Consumers or users may include individual consumers, patients, physicians and hospitals.

2. Retail Level: - recall to the level immediately preceding consumer or user level. It includes retail groceries, pharmacies, hospital pharmacies, dispensing physicians, institutions such as clinics and nursing homes, etc.

3. Wholesale Level: all distribution levels between the manufacturer and retailer.

6. SOUTH AFRICA^22-24:

6.1 INTRODUCTION:

Recall - means the removal of specific batch/batches of a medicinal product from the market for reasons relating to deficiencies in the quality, safety or efficacy.

The guidelines for recall/withdrawal of medicines are the result of an agreement between the holder of the certificate of registration/parallel importer of the medicine and the Department of Health: (Medicines Control Council) (MCC) in South Africa.

6.2 RECALL CLASSIFICATION:

Recalls are classified into both the class according to the level of health hazard involved (risk to the patient) and type which denotes the depth or extent to which the product should be recalled from the distribution chain, e.g., Class I, Type C recall, etc.

● Class I is for defective/dangerous/potentially life-threatening medicines that predictably or probably could result in serious health risk/adverse events or even death.

● Class II is for medicines that possibly could cause temporary or medically reversible adverse health problems or mistreatment.

● Class III is for medicines that are defective and are unlikely to cause any adverse health reaction or which do not comply with the requirements of Act 101 of 1965 in terms of the requirements of printed packaging material, product specification, labelling, etc.

● Type A recall is designed to reach all suppliers of medicines (all distribution points) i.e. wholesalers throughout the country, directors of hospital services (private as well as state hospitals), retail outlets, doctors, nurses, pharmacists, authorised prescribers and dispensers and individual customers or patients through media release (radio, television, regional and national press). Action: Recall letter to all distribution points plus media release.

● Type B recall is designed to reach wholesalers throughout the country, directors of hospital services (private as well as state hospitals), retail outlets, doctors, nurses, pharmacists, authorised prescribers and dispensers. Action: Recall letter to all distribution points.

● Type C recall is designed to reach wholesale level and other distribution points (e.g., pharmacies, doctors, hospitals) this can be achieved by means of a representative calling on wholesalers and/or retail outlets. If it is known where the product in question had been distributed to, specific telephone calls or recall letters to arrange for the return of the product could be made. Action: Specific telephone calls, recall letters to/representatives calling at distribution points if known where the medicines have been distributed.

6.3 LEVEL OF RECALL:

There are three levels of recall such as consumer/user, retail and wholesale.

● Consumer or User Level: Consumer or user may include individual consumers, patients, physicians and hospitals.

● Retail Level: It includes retail groceries, pharmacies, hospital pharmacies, dispensing physicians, institutions such as clinics and nursing homes, etc.

● Wholesale Level: all distribution levels between the manufacturer and retailer.

Figure 4: Number of drug recalls happened in the last three years in South Africa.

7. CONCLUSION:

Drug product recall is not a desirable event for any pharmaceutical company. Also recalling a product is not an easy task once released into the market as recovery from different levels is a difficult and tedious job. Recall of any product adversely affects the financial status and commercial goodwill of the manufacturing company. The regulatory bodies ensure proper fulfilment of recalling by implementing strict guideline defining procedure²⁵ from notification to termination. Recalling can be done smoothly when company management follows guidelines, and does all the recalling activities as defined.

In developing countries like the US, Canada there are specific guidelines and regulations for drug recall procedure and a large number of drugs are recalled due to various reasons but in India and South Africa there are less number of drug recalls as compared to US and Canada due to less regulations. So, to get safety and efficacy of drugs both the countries have to implement the regulations properly.

It is essential to launch the drug in the market after assuring the safety and efficacy of the new intervention so as to minimize drug product recall. Major drug recall list of history suggests that lots of carelessness is involved during the drug development and manufacturing period. The long list of drug recalls on FDA website is evidence that still industries are not following the standard guidelines issued by FDA.

Majority of drug recalls occur in the United states due to various reasons. In 2020-2022 total 257 drugs were recalled in Last three years. In Canada and Australia 220 and 25 drugs are recalled respectively. India²⁶and South Africa have recalled 2 and 21 drugs respectively. By the observation we can conclude that India and South Africa have a smaller number of recalls due to lack of recall regulations. In the USFDA number of drug recalls are decreasing due to following up the laws and regulatory.

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Received on 16.12.2022 Modified on 08.02.2023

Asian J. Pharm. Res. 2023; 13(2):99-104.

DOI: 10.52711/2231-5691.2023.00020