Introduction
Quality is the characteristic of a service or a good to be fit for use by the customer or the consumer. The pharmaceutical quality means the production of a product that is free of contamination that gives the therapeutic benefit that is labeled in the container to the customer. This quality is either evaluated in vitro or vivo by the tests performed. In quality design, the vitro product is ensured to have good performance and the same provide a similar quality in the vivo performance test. In this case, the product performance is related to the product performance.
Quality by Design (QbD)
This is an approach that is used to ensure that the conduct, planning, analysis and reporting of the clinical activities are done in such a way to eliminate the errors of the matter. To implement this, the QbD develop predefined aims that emphasize on the product and process involved in controlling about sound science and quality risk management. The quality by design approach is implemented to enhance the safety, effectiveness and manufacturability of the drug supplied to the customer. The process of QbD requires appropriate tools such as process analytical technology (PAT), risk assessment, and design of experiments in its implementation to achieve the desired quality.
Quality Target Product Profile (QTPP)
This is a summary of the quality properties of the drug product that will be obtained and taking into consideration the safety and efficacy of the product. These properties include; the form of dosage and strength, container closure system, indication of the route administration, the attributes the affect the pharmacokinetic features and the finished pharmaceutical product (FPP) criteria (askaboutgmp.com, 2012)
Critical Quality Attributes (CQA)
This is a chemical, biological, physical or microbiological property of the process that has appropriate limits, range or distribution to ensure the desired quality in a product.
Critical Process Parameters (CPP)
These are steps with a variability that has an effect on the critical quality attribute and hence should be controlled or monitored to allow the realization of the desired quality.
Quality Risk Management (QRM)
This the process of identifying the risks involved in activity and taking the necessary steps to control them and reviewing the results to improve the quality.
Both quality management and quality design assess and manage risks then they improve the activities in a particular set up. Ina pharmacy setup the monitoring of may involve the following activities. The issues related to the progress of the physician are discussed. The physician does not provide any note regarding the visits made by the patients. These suggestions and others relating to the quality of services offered are acted upon for improvement (Hanes, Wong, and Saini, 2013)
Processes and Principles of Quality by Design development
There are several steps that are involved in the processes in meeting the Quality by design objective. Firstly, the product in question is described to provide information that pertains it use, safety and efficacy of the item. Secondly, the quality profile of the product is defined to outsource information that will be used by the process engineers as a quantitative surrogate for feature relating to the efficacy and clinical safety of the product during its development. Thirdly, the information concerning the use of drug, process operations and potential excipients are gathered into a knowledge space, and the risk assessment technique is used to give the priority to the knowledge gaps for further investigation. The fourth step involves the formulation and identification of the attributes of the critical material and of the final product parameters that should be controlled to realize the targeted quality profile. This is followed by designing of the manufacturing process that will generate the final product that possesses all the desired critical qualities. The next step is the identification of the critical process parameters and the raw material features that must be inputted and controlled to meet the final product necessary measurements. The risk assessment is used to prioritize this input parameter and material attributes for experimental verification. The initial knowledge and the experimental results are then compared to establish the design area for process understanding. Finally, a control strategy is for the whole processes established to ensure a good quality final product. The strategies that are put in place for controlling are; process controls, material controls and monitors of design spaces in the individual or multiple unit operations of the final product tests. It should also be noted that the control strategy must include unexpected changes in the scale as directed by the risk management strategy. The process is updated and monitored continually to maintain consistency in quality (askaboutgmp.com, 2012)
Difference between Traditional approach and Enhanced QbD approach
The following table shows the difference in the above two approaches of quality by design in parameters of aspect, current and quality design by the approach.
(askaboutgmp.com, 2012)
Advantages of QbD
The benefits of QbD in the industry are; less batch failure, a better understanding of the process, the high value of cost savings/return on investment and a more efficient technique in the production of a quality drug.
Management and personnel function/structure of a pharmaceutical manufacturing site
Introduction
An organizational structure refers to how individuals and team activities in an organization are coordinated and managed. The activities of the organization require proper coordination and management if the goals and objectives of the company are to be realized. A structure a tool is valuable in obtaining coordination since it specifies the reporting relationships, description of linkage of various operations and communication delineation of channels. An organization can work with different structures each having unique advantages and disadvantages. In a pharmaceutical firm the following organization chart in figure 1 is commonly used. Each department or unit has specified roles that perform to achieve the organization goals. The words in bracket show the job title regarding the department (Arruñada, 2004)
Research and Development (Product Development Lead)
This department is responsible for generating new medications/drugs and installing the same on the disease fighting collections of physicians. The processes involved here are incubation of new ideas, doing research on them and identifying the chemical compounds needed for the production of the drug. In these criteria, thousands of candidate raw materials are picked for selection based on the desired properties using the modern computerized tools. The candidate materials are approved by first passing them through the body and allowing them to react with the required pathology. The candidates are then optimized via changing their chemical composition structures to decrease their side effects while increasing their medicinal effect. Phase tests are then carried out to determine if the drug is safe for experimenting with a human being. The remaining candidate drugs are put through clinical trials which are the final but the longest step (Opsdog.com, 2016)
Pharmaceutical Manufacturing (Plant Manager)
The department is responsible for the drug production on an industrial scale by following the clinical trials and tests that have been approved by the regulatory board. The processes involved here are chromatography, milling, granulating, coating and pressing. However, there are other activities done in production apart from the ordinary steps listed above. These are quality assurance, facility maintenance, batch integrity testing and other supporting manufacturing operations. The active pharmaceutical ingredients can be produced by some pharmaceutical manufacturing firms while the rest buy them in bulk from suppliers. These will require some preparation for consumption by addition of certain compounds such as binders and fillers (Opsdog.com, 2016)
Clinical Trials (Clinical Research Coordinator)
This is the most expensive and lengthy phase of the new drug research and development. The policy of Food and Drug Administration (FDA) demands the testing of the candidate pharmaceuticals. This test involves the passage through a three-phase of human tests/trials to show the safety and the baseline efficacy. The first phase requires a small number of test patients while the last phase needs thousands of test patients and the process is very expensive. The desired statistic is 90 % certainty the drug meets in the last phase (Opsdog.com, 2016)
Product Compliance (Compliance Manager)
The function of this department is to organize the licensing of the drug. They are also responsible for education and information management and subsequent labeling of the product. All the drugs are ensured that to be labeled according to preset requirements of FDA and that proper marketing materials are used in reaching to the potential physicians and patients. This group may perform some audit on company operations such manufacturing and drug testing to ensure compliance with the industrial regulations (Opsdog.com, 2016)
Patient services (Patient Service Representative)
The department works together with the insurance companies and physicians all the processes of pharmaceutical products distribution are availed and fully utilized. Their duty is to educate the insurers and the physicians on the plans of treatments and provide information such consultations referrals and any other useful treatment information. The product I brought to the market with strategies laid on the distribution in the market. After successful passing of clinical trials and licensing, a reimbursement study is initiated by the company. This is called the ‘Phase IV Testing. In this last phase, the drug is economical scales of the drug are evaluated before releasing it into the market (Opsdog.com, 2016)
Patient Assistant Programs (Patient Assistance Coordinator)
These are initiatives that are funded by the company to distribute reduced-rate or free drugs from low to medium income earners who are underinsured. In this case, the patient may be insured or uninsured (Opsdog.com, 2016)
Active Pharmaceutical Ingredients (API)
These are substances that are incorporated into drugs and that are responsible for implementing the beneficial health benefit in the sick person or consumer. One of the examples of API is the acetaminophen that is contained in a pain relief/killer tablet. The quality of these ingredients in a drug substance has a direct impact on the safety and the performance characteristics of the drug. The poorly manufactured and contaminated API in the drug is known to yield negative health results including death. For this reason, the manufacture of the API has been regulated worldwide. In an API, the structures, and the solid/liquid state conditions are the major contributions to their physical and chemical properties (Mdtvalliance.org, 2013)
Chemical Components of API
Rifampicin
The main degradation of API and comes from the hydroquinone group which facilitates the solubility in the alkali medium. The tertiary amine is prone to oxidation and enhances solubility in the acidic medium. The hydrolysis of this compound is facilitated by hydrazine which yields formally rifamycin on hydrolysis. The other compound that hydrolyses is the 25-acetyl group which is converted to 25-desacetyl rifampicin on hydrolysis. The presence of the unsaturated molecule enables its sensitivity to light (Mdtvalliance.org, 2013)
Identification test C
In the infrared region in a test, the IR absorption spectrum is concordant the one obtained from the anhydrous nevirapine RS or with its spectrum. In testing the hemihyrate, the IR absorption depicts a sharp absorbance at 3503/cm and after heating for one hour at 1400C followed by cooling, the infrared absorption spectrum becomes concordant with the anhydrous nevirapine spectrum or its reference.
API stability tests
The relative humidity of indivar is 60% and therefore, it is highly hygroscopic.
When the moisture content or high temperature are is present in during manufacture, the API changes to an amorphous material or to anhydrate crystal form and product formation (Mdtvalliance.org, 2013)
Types of APIs
Gembfibrozil
The name is referring to the drug used for lowering the levels of lipids in the body. The drug is effectively administered for treating hypertriglyceridemia and hyperlipidemia and is normally marketed under the name Lopid. Its chemical formula is C24H34N4O5S.
The drug is an activator of or nuclear receptor that is involved in the metabolism of fats and carbohydrates. Another function done by the drug is the differentiation of adipose tissue. The effect of this drug is the reduction of the levels of very low density of lipoprotein (VLDL) and a little reduction in low-density lipoproteins (LDL)
Precautions for Drug use
People suffering from renal or hepatic disfunction should not take Gemfibrozil. Care should also be taken by guys with obese patients, Native Americans, biliary tracts disease and pregnant women.
Azithromycin API
This is an antibiotic used for the treatment of skin, ear and chest conditions. This drug inhibits synthesis of bacterial protein by binding to the 50S ribosomal part of the bacterial 70S type of ribosome. Its market brand is Zithromax and is produced by the largest pharmaceutical company Teva API.
Mechanisms of action
The drug interferes with the synthesis of bacterial protein binding firmly to the 50S subunit of bacterial ribosome and hence inhibiting it from turning to mRNA. Its long life also helps in its functionality since daily doses or short term doses can be administered.
Side effects
A few people are susceptible to vomiting, nausea, and diarrhea (Mdtvalliance.org, 2013)
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