Pharmaceutical Drug Product Development and Process Optimization

Effective Use of Quality by Design

Sarwar Beg, Majed Al Robaian, Mahfoozur Rahman, Syed Sarim Imam, Nabil Alruwaili, Sunil Kumar Panda, Sarwar Beg, Majed Al Robaian, Mahfoozur Rahman, Syed Sarim Imam, Nabil Alruwaili, Sunil Kumar Panda

• Editorial: Apple Academic Press
• Año: 2020
• ISBN:
  9781000731583
• Edición: 1
• Categoría: Betriebswirtschaft
• Categoría: Pharma-, Biotechnologie- & Gesundheitsindustrie

Pharmaceutical manufacturers are constantly facing quality crises of drug products, leading to an escalating number of product recalls and rejects. Due to the involvement of multiple factors, the goal of achieving consistent product quality is always a great challenge for pharmaceutical scientists. This volume addresses this challenge by using the Quality by Design (QbD) concept, which was instituted to focus on the systematic development of drug products with predefined objectives to provide enhanced product and process understanding.

This volume presents and discusses the vital precepts underlying the efficient, effective, and cost effective development of pharmaceutical drug products. It focuses on the adoption of systematic quality principles of pharmaceutical development, which is imperative in achieving continuous improvement in end-product quality and also leads to reducing cost, time, and effort, while meeting regulatory requirements. The volume covers the important new advances in the development of solid oral dosage forms, modified release oral dosage forms, parenteral dosage forms, semisolid dosage forms, transdermal drug, delivery systems, inhalational dosage forms, ocular drug delivery systems, nanopharmaceutical products, and nanoparticles for oral delivery.

CHAPTER 1

Introduction to Pharmaceutical Product Development

RAHUL SHUKLA^*, MAYANK HANDA, and VISHWAS P. PARDHI

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh – 226002, India

*Corresponding author. E-mail: [email protected]

1.1 INTRODUCTION

The development of a new pharmaceutical product is the need of time to address the rising pressure on pharmaceutical industries for introducing new clinical candidates in the drug discovery pipeline. The number of pharmaceutical products in the market is increasing at a tremendous rate and the pharmaceutical industry is playing an immense role in it. After the discovery of a new chemical entity (NCE), it is handed over to the product development team of the industry for further development of the dosage form (Bauer and Brönstrup, 2014). The newly discovered NCEs can be developed as an immediate release product, sustained-release product, injectable, topical or transdermal and so many other forms by considering the factors such as nature of the disease (acute or chronic), site of action, the onset of action, patient condition and critical physicochemical properties of the NCE. Table 1.1 provides information on the annual revenue of top-ranked pharmaceutical companies globally. The giant pharmaceutical companies are mainly indulging in drug discovery programs most of the time encounter a problem of product failure while producing the commercial batch if sufficient biopharmaceutical factors are not considered during the developmental phase. These factors lead to economy loss, manpower and time to identify the root cause and rectification of product failure. Thus, the development of new drug products necessitates thorough knowledge of pharmaceutical sciences to avoid such losses (U.S. Department of Health and Human Services Food and Drug Administration, 2009). Figure 1.1 provides an illustrative presentation of drug discovery.

TABLE 1.1 Annual Revenue of Globally Top Ranked Pharmaceutical Companies

Global Ranking	Company	Revenue in year 2017 (in US billion $)^*
1	Pfizer	52.54
2	Roche	44.36
3	Sanofi	36.66
4	Johnson & Johnson	36.30
5	Merck	35.40
6	Novartis	33.00
7	AbbVie	28.22
8	Gilead Sciences	25.65
9	GlaxoSmithKline (GSK)	24.00
10	Amgen	22.85

FIGURE 1.1 Illustrative presentation of drug product development.

Product development is a broad term that covers a wide spectrum of the products varies from different pharmaceuticals, medical devices, diagnostic kits, and surgical products. There are many products available in the market with different prices from different manufacturers according to the need of the customers (Politis et al., 2017). In the case of pharmaceutical products, a single NCE can be available in the different dosage forms depending upon the target population based on gender, age, patient conditions, and clinical needs. Pharmaceutical product development is a multistep process that initiates from the triggering of an idea followed by the conception which finally leads to the formation of the product. It usually takes approximately 20 years of time and the expenditure of a huge amount of money for a drug product to reach in the market through the vast process of drug discovery, clinical phase, and product development. In simple words, we can say that pharmaceutical product development is the process of development of converting the NCE into the drug product which can be comfortably consumed by the patient with a dose to elicit the desired therapeutic effect (Program et al., 2008). Table 1.2 provides information on top-selling brands and its revenue globally.

1.2 DRUG DISCOVERY

The sojourn journey of the NCEs which are therapeutically applicable in mitigation and cure of diseases from discovery laboratories to the shelf of retail shops and in the hands of the patient is the successful drug discoveries. Efforts of drug discovery start very first from the initial stage of identifying the biological target and identification of lead molecules which paves the foundation stone for the synthesis of molecules and finally leads to product development. Drug discovery is a multistep process starting from target identification to the lead optimization followed by pre-clinical and clinical trials. First of all, an effective biological target is selected which plays an important role in the disease (Bauer and Brönstrup, 2014). The next step in the process of drug discovery is the synthesis of the compounds, characterization of compounds, in vitro screening followed by pre-clinical and clinical trials. The average time for drug development is 10–15 years and the average cost of drug development varies from US$ 1.5 billion to US$ 1.9 billion. Due to the high cost of R&D and human clinical trials, the process of drug discovery and development is very costly (Zhao et al., 2006a). A graph depicting various stages in the product life cycle is mentioned in Figure 1.2. Table 1.3 is the information of patented molecules going to expire in the year 2018. In the current era, the developing countries are suffering from many infectious diseases and the number of treatments available for these diseases is very less. It was noted in the past that most of the drugs are discovered either by traditional methods of drug discovery from natural resources or by serendipity. At present, novel approaches of drug discovery are followed which starts with target identification based on the disease by employing various tools such as combinatorial chemistry, cell-based assays, high throughput screening and computer-based (in-silico) studies (Zhao et al., 2006a; Katsila et al., 2016). Various phases of product development are given in Figure 1.3.

TABLE 1.2 Annual Revenue of Top Most Selling Brands Globally

Global Ranking	Brand	NCEs	Company	Revenue in year 2017 (in US billion $)^*
1	Humira	Adalimumab	AbbVie Inc. (USA)	18.43
2	Eylea	Aflibercept	Bayer (Germany) & Regeneron Pharmaceuticals (USA)	8.23
3	Revlimid	Lenalidomide	Celgene (USA)	8.19
4	Rituxan	Rituximab	Biogen & Roche	8.11
5	Enbrel	Etanercept	Amgen Inc. (USA) & Pfizer (Europe)	7.98
6	Herceptin	Trastuzumab	Roche	7.55
7	Eliquis	Apixaban	Bristol-Myers Squibb (USA) & Pfizer (USA)	7.40
8	Avastin	Bevacizumab	Roche	7.21
9	Remicade	Infliximab	Johnson & Johnson (USA) & Merck (USA)	7.16
10	Xarelto	Rivaroxaban	Bayer (Germany) & Johnson & Johnson (USA)	6.54
11	Januvia/Janumet	Sitagliptin	Merck	5.90
12	Lantus	Insulin glargine	Sanofi	5.65
13	Prevnar 13/Preventer	Pneumococcal 13-valent conjugate Vaccine	Pfizer	5.60
14	Opdivo	Nivolumab	Bristol-Myers Squibb	4.95
15	Neulasta/Peglasta and Neupogen/Gran	Pegfilgrastim and Filgrastim	Amgen (USA) & Kyowa Hakko Kirin (Japan)	4.56
16	Lyrica	Pregabalin	Pfizer	4.51
17	Harvoni	Ledipasvir/Sofosbuvir	Gilead Sciences	4.37
18	Advair/Seretide	Fluticasone and Salmeterol	GlaxoSmithKline	4.36
19	Tecfidera	Dimethyl fumara...