A Research on Patient Safety: Importance of In-process Quality Control Testing and the result of poor training of operators in Pharma Industry

Jyodish S S.¹*, Abinaya G.², Ashlesh Prabhu.³, Muddukrishna B S.⁴, Mahendra Joshi.⁵,

Kiran Kumar H.⁶, Girish Pai K.⁷

¹Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal, Karnataka, India – 576104.

^2,3,7Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal, Karnataka, India – 576104.

⁴Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences,

Manipal Academy of Higher Education, Manipal, Karnataka, India – 576104.

⁵Research and Development, IDRS Labs Pvt. Ltd., Bangalore, Karnataka, India.

⁶Corporate Development, Ingenus Pharmaceuticals LLC, 100 Ford Rd, Denville, New Jersey.

*Corresponding Author E-mail: girish.pai@manipal.edu, jyodish21@gmail.com

ABSTRACT:

To achieve successful therapeutic results, patient compliance with prescribed treatments is essential. Compliance can be assessed in two primary ways: indirectly through the patient's self-report or directly through chemical analysis of physiological fluids. Indirect methods such as self-reporting are commonly used due to their simplicity and ease of administration. However, direct methods, including laboratory analysis of bodily fluids for the presence of drugs or their metabolites, offer a more accurate measure of adherence to prescribed therapy. Complicated drug regimens, particularly those involving multiple medications or complex dosing schedules, often result in significant challenges for patients. These challenges can include a lack of understanding of the treatment, inadequate health literacy, and the occurrence of side effects. To mitigate these challenges, strategies such as providing medication reminders, streamlining prescription programs, and offering patient education and training can be employed. These interventions help to improve patient understanding, ensure timely medication intake, and foster better adherence. Ensuring the safety of medications is also critical to patient compliance. Pharmaceutical companies must implement rigorous quality control measures to guarantee that drugs are safe and effective. Defective products, such as nasal spray actuators that break easily, medications without batch codes, or improperly packaged pills, can pose serious risks to patient health. Investigating and addressing these production defects is crucial. Potential patient hazards, such as incorrect dosages or contamination, must be identified and rectified through corrective actions. Quality control systems and patient-centered approaches in healthcare, supported by regulatory agencies such as the FDA, are necessary to safeguard drug quality and patient safety, ultimately improving therapeutic outcomes.

KEYWORDS: Patient Compliance, FDA drug recalls, Pharmaceutical defect, QA inspection, IPQC.

INTRODUCTION:

Compliance is defined as "The number of doses not taken or taken incorrectly that risk the therapeutic outcome"¹. Additionally, self-reporting or a patient interview can be used to assess compliance. Measures of compliance are both direct and indirect. Direct compliance measures are usually used to detect a chemical in body fluids². Indirect measures of compliance are more frequently reported in the literature, probably because these indicators are easy to obtain³. Behavioral and instructional techniques are the tactics used to improve compliance. Patient compliance is critical for both the manufacturer's and patient's safety. For manufacturers, it assures product effectiveness, provides accurate information for regulatory approval, and preserves their recognition⁴. Both producers and healthcare vendors can increase treatment success and safety by educating patients and providing tools to improve compliance⁵.

Strategies To Improve Patient Compliance:

1. Promote Patient Education:

An essential factor in enhancing patient adherence is the education of patients. By providing clear and comprehensive information about their condition and treatment process, patients' engagement and dedication to their treatment plans can be significantly enhanced. Written materials, instructional films, and interactive web tools are a few examples. Improved knowledge of the drug, along with their motivation and attitudes toward the recommended course of treatment, can assist in reducing noncompliance with pharmacological therapies.

2. Lower the obstacles to compliance:

Improving overall compliance requires an understanding of and recognition of the possible obstacles that lower patient compliance. According to research, up to 40% to 70% of patients may not follow treatment recommendations, especially when it comes to complicated regimens or lifestyle modifications.
The following are significant obstacles to compliance:

· Complicated drug schedules

· Inadequate knowledge of health

· Lack of information regarding the benefits of treatment.

· Unnoticed adverse effects

· Unsatisfactory treatment 

· The price of pharmaceutical drugs

3. Boost Patient Compliance:

Compliance can also be increased by streamlining treatment plans. To make it easier for patients to follow their prescribed pharmaceutical schedule, healthcare practitioners may choose to use long-acting formulations, combination pills, or once-daily dosing. These are examples of best practices, whenever feasible. This approach can be facilitated using pill counts and other measure compliance methods.

It has been demonstrated that better drug packaging, such as dose strips and blister packs, greatly increases patient compliance⁶.

4. Utilize One-on-One Conversations and Reminders:

Patients can benefit from reminders given by phone, email, or text message; just make sure they give their permission to receive such communications.

Patient compliance can be significantly improved by creating a collaborative and encouraging healthcare atmosphere. Healthcare professionals can boost patient happiness and enhance adherence results by cultivating a patient-physician relationship that values the patient's autonomy and promotes active participation in their care.

Finally, employing behavior modification techniques might enhance adherence. This might consist of:

· Having reasonable health objectives

· Giving adherence and encouraging feedback

· Reminder systems are used to assist patients in remembering their appointment times and prescription dosages.

FDA recalls are also an important thing to overcome patient compliance.

The most effective way to safeguard the public from a defective or possibly hazardous product is through a drug recall. A recall refers to a voluntary choice by a company to withdraw a defective medication from the market or notify customers and patients about a potential risk^7,8.

It consists of 3 types.

Figure 1. Types of recall⁹

Table 1. Recent FDA recalls

Date and company name	FDA Recall Product Name	Reason for Recall	Type of Recall
May 31, 2018 Apotex Corp.	Fluticasone Propionate Nasal Spray, USP, delivers 50 mcg with each spray and contains 120 metered sprays.	Presence of small glass particles in Fluticasone Propionate Nasal spray. The glass fragments may obstruct the actuator and affect the pump's operation. It inflicts localized damage to the nasal mucosa that could happen with the use of the faulty product^10.	Class II recall
November 19, 2024 Endo, Inc.	Clonazepam Orally Disintegrating Tablets USP (C-IV)	Possible inaccuracies in labeling the strength of product cartons and incorrect National Drug Code (NDC) on cartons due to third-party packaging errors^11.	Class II recall
March 27, 2024 Amneal Pharmaceuticals, LLC	Vancomycin Hydrochloride for Oral Solution USP, 250 mg/5ml	Super potent due to overfilled bottles leading to the risk of overdosing^12.	Class II recall
February 27, 2020, American Health Packaging	Ranitidine Tablets, USP 150 mg (American Health Packaging)	NDMA (Nitroso dimethylamine) impurity, above FDA-established levels^13.	Class II recall
March 01, 2019 Apotex Corp	Drospirenone and Ethinyl Estradiol Tablets, USP 28x3 Blister Pack/ Carton (Apotex Crop.)	Possibility of missing/incorrect tablet arrangement and/or an empty blister pocket^14.	Class II recall

Case Study 1 – Nasal Spray, Malfunctioning In Actuator¹⁵

Dosage form: Nasal spray

Generic Name: Fluticasone furoate nasal spray

Therapeutic category: Corticosteroids (eases breathing)

Defects: Malfunctioning of nasal spraying actuator (product not getting released while using the container)

Category of complaint: Critical¹⁶

Probable root causes:

Malfunction of pump/actuator either due to defective spring assembly or the possibility of blockage of the orifice due to drying of product.

Remediation:

· Better control of the pump performance/actuator assembly at the supplier end

· Cleaning of the pump with warm water procedure to be described in patient information leaflet (PIL)

· Proposing the in-use time to avoid drying of product and subsequent blockage.

Figure 2. Defective nasal spray intact container

Clinical Significance:

· The malfunctioning of the actuator of the nasal spray fails to deliver the required quantity of fluticasone. This will lead to altered therapeutic efficacy or therapeutic failure. Finally, not suitable for usage.

· Highly problematic for geriatric patients as it is used to ease breathing.

Case Study 2 – Evidence on Missed Batch-Coded Primary Label On Liquid Orals¹⁵

Dosage form: Liquid dosage form (Suspension)

Generic Name: Erythromycin estolate suspension

Therapeutic category: Macrolide Antibiotic

Defects: The primary label did not have any batch over coding details.

Category of complaint: Critical¹⁶

Probable root causes:

· A manufacturing fault occurred during the over-coding process.

· Insufficient quality control before release.

· There is no mechanism based on cameras to guarantee over-coding.

· During the labelling process, the stereo over-coding falls off.

Remediation:

· Better supervision during labelling operation.

· A camera-based system is being installed to make sure that bottles without excessive coding are rejected.

· Improved visual inspection and cartoning rules to guarantee that bottles without over-coding are automatically rejected.

· Installing an alarm-based camera system will notify the operator when the labelling process is not correctly performed.

Figure 3. Evidence for missed batch coded primary label

Figure 4. Close-up image showing the defect

Clinical Significance:

· In the event of any adverse events or efficacy-related problems resulting from product-related quality difficulties, it may be difficult to identify the product.

· Product recalls will be difficult if the label does not include the batch number¹⁷.

Case Study 3 Half Tablet Found Within Intact Blister Packet (Right Side 4^TH Tablet)¹⁵

Dosage form: Film-coated tablets

Generic Name: Ivabradine tablets 5 mg

Therapeutic category: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker

Defects: Only half of the film coated tablet found within intact blister pocket.

Category of complaint: Critical¹⁶

Probable root causes:

· IPQC checks were not done adequately.

· Intermediate product line clearance was not properly performed.

· Final QA line clearance was given without proper inspection¹⁸.

Remediation:

· IPQC check should be carried out adequately.

· QA line clearance should be done before starting the packaging and with predetermined time points.

· A sensitive camera should be installed in the blister packing equipment to capture broken tablets in the blister.

Figure 5. Half tablet found within intact blister pocket (right side, fourth tablet)

Clinical significance:

· Patient acceptance will decrease and directly affect the therapeutic outcome due to the psychological effect. Altered therapeutic efficacy due to decreased active ingredient.

· Reduced bioavailability due to altered dissolution or stability of the active ingredient and release profile of the tablet will be lost.

Case Study 4 – Two Tablets Within Single Blister Packet [Right Side]¹⁵

Dosage form: Film-coated tablets.

Generic Name: Sildenafil citrate tablets

Therapeutic category: Treatment of erectile dysfunction.

Defects:

 Two tablets packed within one intact blister pocket¹⁹.

Category of complaint: Critical¹⁶

Probable root causes: Due to tilting, two tablets entered the delivery channel because of the improper placing/setting of the safety cover.

Remediation:

· Better visual inspection, probably with a sensitive camera and safety channel placing to be monitored.

· Better visual inspection by packing line and IPQC personnel.

Figure 6. Two tablets within a single blister pocket

Clinical Significance:

· Market value of product and label claim non-compliance.

· Patients may take both tablets by mistake, leading to serious adverse effects.

· Blister may fail for leak test (aluminum foil having pin holes) as crimping may affect the sealing quality leading to degradation of product especially when the drug is hygroscopic.

CONCLUSION:

Patient compliance is a fundamental factor in achieving successful therapeutic outcomes, yet it is often challenged by complex regimens, inadequate health literacy, and medication-related barriers. While both direct and indirect assessment methods play a role in monitoring adherence, ensuring medication safety through stringent quality control is equally crucial. Defective pharmaceutical products not only compromise efficacy but also endanger patient health, emphasizing the need for continuous oversight and regulatory enforcement. By integrating patient-centered strategies- such as education, reminders, and streamlined prescription processes- alongside robust quality assurance measures, healthcare systems can enhance adherence, minimize risks, and ultimately improve patient well-being. A commitment to both compliance support and medication safety is essential for optimizing treatment success and advancing public health.

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Received on 17.04.2025      Revised on 11.11.2025

Accepted on 06.04.2026 Published on 20.05.2026

Available online from May 25, 2026

Research J. Pharmacy and Technology. 2026;19(5):2014-2018.

DOI: 10.52711/0974-360X.2026.00288

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