**1. Introduction**

The United States of America (USA), Europe and Japan were developed the Common Technical Document (CTD) which should be implement while applying for registration of pharmaceutical product for human use. For the development of these guidelines International conference for Harmonization (ICH) plays important role and currently these are becoming the part of ICH guidelines [1]. The identity, strength, quality, purity and potency are important points of Investigational new drug application (IND), New drug application (NDA), Abbreviated new drug application (ANDA). The related analytical methods of drug substance and product should be included in NDA and ANDA. A Complete description, total manufacturing process including analytical procedures should

ensure compliance with standards and potency should be part of Biologics license application (BLA). It is must to meet all standards of guidelines provided for analytical procedures. All these parameters should be suitable for their purpose wherever applicable. Detail Analytical procedures including detail validation parameters are the important part of Electronic Common Technical Document Specification as per International conference of Harmonization (ICH). The analytical procedure is Food and Drug Approved (FDA) if it a part of Approved NDA, ANDA or BLA. These methods can be generated from FDA recognized sources like U. S. Pharmacopeia/National Formulary (USP/NF) or if anyone submits validated procedure that will be accepted by FDA. The only validation or verification data of FDA approved methods of new products are considered for applications to various drug products (**Figure 1**).

Every manufacturer must generate large amount of corrected data for safety and efficacy of drug for commercial viewpoint. As it is mandatory to follow Current Good Manufacturing practices (cGMPs) for manufacturing purpose, likewise each analytical activity must follow Good Analytical Practices.

Method Validation, calibrated instrument, and training are three important tasks of Good analytical practices (GAPs). Commercially available dosage form is an outcome of several steps which are systematically carried out during product development. It is very important that all steps should be carried in systematic manner to ensure complete drug development stage. In recent years there is special focus on efficiency and efficacy of drug product and for this clinical study is most important task but apart from this there are various behind the scene activities are associated with drug development process without which pharmaceutical drug development is not possible. Among these behind the scene activities Method Development and Validation has its own uniqueness to ensure the drug development.

**153**

*Analytical, Bioanalytical, Stability-Indicating Methods: Key Part of Regulatory Submissions*

The objective and plan of work should be clearly defined prior to start the work. This data is based on scientific findings from the method development and Optimization. The validation of results should be obtained by approved protocol. Then sponsor must follow cGMP's which includes detail procedure, validation characteristics and acceptance criteria by the use of qualified instrumentation. All the protocols of drug substance and product analytes in respective matrices should be prepared and followed. All the results of validation studies, application should be included.

The analytical procedure official in pharmacopeias, are cross checked for implementation stage and its suitability should be checked. The verification protocol should include details of data which explains suitable analytical procedure official

1.The compendia method which should be verified with acceptance criteria's.

2.All parameters related to each aspect of method that is reagent, equipment, validation characteristics that is specificity, Limit of quantitation (LOQ ), Precision, accuracy, should be included in validation are covered by procedure and extent of verification. There is no need to include robustness study for compendia assays if there is no deviation. For a BLA, if the methods are already specified in FDA regulations, there is must to take pre-approval from

The statistical analysis is important work after finishing the method development and validation. The statistical values of validation are compared with the

The statistical parameters used are based on proper principle and required for evaluation of parameter. The methods like analysis of variance (ANOVA) for analysis

for studying validation characteristics. In case of observed data is not distributed then it is transformed normal distribution or distribution free approach. By using validates

software or independent verification for correctness the data can be analyzed.

parameters are depending on method or procedure under validation. System suitability can be evaluated according to following points:

Before starting actual analysis of standard sample, it is necessary to check whether system is working properly or not. This important task can be completed by analyzing system suitability. In this all integral system that is equipment, electronics, analytical operations and samples are evaluated. These system suitability

1.The system suitability measures the performance of given system of samples on a given day. 2. The variable parameters like chromatographic columns, column aging, mobile-phase variations, changes in instrumentation are checked

**3.2 System suitability requirement for potency assay**

whether they are working properly or not.

The following points are to be included in the verification protocol

*DOI: http://dx.doi.org/10.5772/intechopen.93566*

**3. Compendial analytical procedures**

in USP/NF for drug product or drug substance.

FDA to change in analytical method.

**3.1 Statistical analysis**

of regression analysis, (R2

predetermined acceptance criteria.

**2. Noncompendial analytical method validation**

**Figure 1.** *Flow chart showing essential requirements of registration of pharmaceutical product.*

*Analytical, Bioanalytical, Stability-Indicating Methods: Key Part of Regulatory Submissions DOI: http://dx.doi.org/10.5772/intechopen.93566*


9. Preventative measures

This gave rise to another scandal, in the area of organic production, with extensive recall actions as a result. The affected companies could be identified exactly in the beginning. The database system developed by KAT at the time, striving to safeguard traceability, as well as the newly introduced identification measures for individual eggs with origin labelling, proved to be an effective preventative measure. For the first time, it was possible to recall contaminated

The affected companies suffered significant losses, even threatening their very existence, but managed to rebuild trust through consistent action-taking. There was an awareness that product traceability is one of the most important food safety criteria in crisis situations. This led to the EC decision to adopt individual egg labelling as a binding requirement for egg

The dioxin crisis of 2011 took place under similar circumstances. Affected companies were closed, and recall actions were initiated. Media pressure was enormous, and consumers were requested to either return or destroy food, primarily eggs and poultry. Thanks to KAT and the mandatory producer code printed on each egg [16], the eggs origins could be traced. The names of the affected companies—publicly traceable through the code—were disclosed by authorities with an accompanying warning. However, the eggs already reached consumers' refrigerators, as the dioxin was discovered in November, but the authorities did not inform consumers of dioxin residue hazards until January 2012. At this point, most eggs were already consumed. Similar recall actions were initiated for poultry; however, this proved to be significantly more difficult as poultry was not distributed using the same traceability system as the KAT individual egg labelling system. This led to immense reputation damage, as well as more critical consumer attitudes, and in turn reduced egg consumption. Interestingly, the organic food industry benefited from this, as consumers expected that the organic industry adhered to stronger regulations and was subject to more stringent controls, improv-

At the end of 2014, the organic food industry was rattled by several events. Residues of a corrosive agent and a fungal toxin were discovered, and the products of numerous companies were stripped of the right to be sold with an organic seal as a result. The contaminated feed, still labelled as 'organic' by a Dutch distributor, had been distributed to organic farmers in

A total of 2000 tonnes of affected feed, sunflower cake, was distributed by a Dutch distributor as organic feed. Organically producing laying hen companies, as well as pig, cattle and sheep

There are no special restrictions for pesticide in place in conventional farming, quite different from organic production, which uses stricter standards. The affected companies faced grave consequences. Goods that had already been delivered were recalled by regional authorities, and goods that were being produced currently could not be distributed for a certain period. It is interesting to note that these regulations were only implemented in individual German states, while the remaining lion's share of cakes contaminated with pesticides could still be processed for organic production in other EU countries. There was no health hazard, but rather

a component in the feed that is not permitted in organic production.

eggs in a targeted manner, avoiding any negative effects or harm to consumers.

distributors across the EU.

14 Food Safety - Some Global Trends

ing safety.

Germany.

farmers, were affected.

Crisis situations can occur suddenly and unexpectedly, even in a carefully managed company. Internal business process problems as well as external, unforeseen difficulties might be the cause. Therefore, a preventative strategy should consider all potential measures that might equip a company to deal with such situations.

This includes general preventative measures (quality measures, self-controlling systems following the HACCP concept principles, traceability, claims and complaints, false management, and the like). Additionally, specific measures should be considered such as the development of a crisis plan and special measures for at-risk products.

Therefore, any properly managed company requires a quality management book, in which the procedural instructions regarding quality politics, as well as the principles of quality assurance, are defined. By now, also in the light of increasing pressure of retailers, systems following the International Feature Standard (IFS) have established themselves. This includes the British Retail Consortium (BRC) [18] and Global Standard for Food Safety, with similar regulations.

A vital component of a quality management system is the aforementioned HACCP concept, which is required following Art. 5 of the Regulation 852/2002 (EC) No. 852/2004 on Food Hygiene. This regulation prescribes that food business operators must develop, implement and maintain one or more procedures based on the HACCP principles.


**5. Conclusion**

Caffeine is a compound that is legal, easy to obtain for the general society, socially acceptable to consume, found in many foods in our daily diet, and generally known for its stimulant properties. Caffeine, whose consumption has increased especially due to the changes in dietary habits in recent years, is a compound that still remains popular today. In this sense, both nutritional caffeine intake and the correlation between caffeine and health have been studied from many different angles. The effects of caffeine consumption on health are still a matter of debate. Although caffeine is generally considered safe except for excessive use in adults, studies on this subject are still insufficient for children and adolescents.

Individuals' daily caffeine intake varies depending on many factors such as the source of caffeine, age of the individual, breed, dietary habits and culture. In general, it can be said that the level of caffeine intake increases in proportion to age, and males consume more caffeine than females. It is understood that coffee and tea in adults and tea, soft and energy drinks in children and adolescents play an important role in caffeine intake.

In the light of the data given in **Table 2** and considering the changes in the consumption patterns regarding foods in recent years, it can be easily said that individuals' daily caffeine consumption is much more than 400 mg/day which is usually considered to be safe. But it should be noted that caffeine intolerance can vary from person to person. Even very small amounts of caffeine can negatively

#### *The Importance of Tea in the Correlation between Caffeine and Health DOI: http://dx.doi.org/10.5772/intechopen.93287*

affect pregnant women, children, the elderly and individuals who are caffeine intolerant. This is why caffeine intake of these individuals should be limited. For this purpose, popularizing caffeine-reduced products on the market can be considered as a strategy for limiting caffeine intake through nutrition. The literature review reveals that tea ranks second in caffeine intake in adults, children and adolescents. Therefore, tea plays a significant role in caffeine intake. But tea has significant differences distinguishing it from coffee, soft drinks and energy drinks that are other sources of caffeine.

Coffee is a drink that is generally perceived as healthy. However, it is also rich in acrylamide that was found out to be contained in food in 2002 and identified by the International Agency for Research on Cancer (IARC) as a possible carcinogen for humans. Carbonated soft drinks and chocolate foods contain many additives in addition to high levels of sugar. Many researchers and institutions approach energy drinks with suspicion due to very high caffeine content. Early acquaintance of individuals with carbonated soft drinks and energy drinks also increases the likelihood of addiction. In general, it can be said that the dietary quality of individuals who consume this type of drink frequently decreases.

Tea is a plant rich in phenolic compounds, especially catechins, and has many benefits on human health due to its antioxidant, antibacterial, anticarcinogen, antimutagenic, and antiallergic effects. Therefore, for conscious consumers, tea is positively different from other foods and drinks due to caffeine and phenolic compounds and is thought to do more good than harm to people. Green tea stands out among tea types with the lowest content of caffeine and high phenolic content.


3.3.3. Natural Fillers

The use of naturally sourced fibre-based fillers, with their considerable tensile strength and high sustainability, presents a key route to facilitating polymer circularity. The hydrophilic nature of bare natural fibres with no surface treatment requires an address, due to the incompatibility with hydrophobic biopolymer. Biopolymer composites reinforced with untreated natural fibres typically exhibit non-uniform fibre dispersion with interfaces promoting crack formation. These material defects can lead to premature mechanical failure of the composites [58,59,96]. These defects are attributable to the natural fibre hydrophilicity, which hinders proper mixing with the biopolymer hydrophobic matrix causing poor fibre/matrix interfacial bonding [59]. While high susceptibility of moisture absorption by the hydrophilic natural fibres can support the growth of fungi and bacteria and deteriorate the physical and mechanical properties of the bio-composites [58], this fact can be a highly useful feature that can be availed of post use for achieving biocyclability.

Different approaches are available to enhance the interfacial adhesion between the fibres and matrix, resulting in the fabrication of biocomposites with better mechanical and barrier properties. Among these solutions is the surface modification of natural fibres. Surface modification can result in increasing the sites of reaction, offering new functionality to the fibre surface and enhancing surface roughness by removing impurities [59]. Such modification will lead eventually to the improvement in mechanical properties and reduction of the water absorption of the fabricated biocomposite. The techniques applied to modify the natural surface fibres before inclusion in biopolymer matrices include physical, chemical, biological treatments and their combinations. Some examples of physical treatment techniques are calendaring, stretching, hybrid yarns production and thermal treatments; while chemical techniques include, alkali swelling, silane modifications, graft copolymerisation, and treatment with isocyanate, mercerisation [97].

A representative selection of the recently applied surface modifications for natural fibres reinforced biocomposites are given in Table 3.

**Table 3.** Surface treatment of natural fibres reinforced bio-composites.

Combinations of natural materials with petroleum-based plastics is an option that is also under development. While facilitating the high mechanical performance, considerations are required when using this approach as further dilemma's may be posed regarding factors, such as continued resource depletion dependencies and degradation and biodegradation pathways, which potentially lead to increased microplastics production.


**Author details**

Humaira Ghazal1 \* and Nadeem Sohail2

1 University of the Punjab, Lahore, Pakistan

2 University of Management and Technology Sialkot Campus, Lahore, Pakistan

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.