chapter 2.3 quality control and assurance in biotechnology

BNN40703Quality Assurance and Quality Control in Biotechnology

By: Dr. Nadirul Hasraf Mat Nayan

CHAPTER 2QUALITY MANAGEMENT,

CONTROL AND ASSURANCE

Chapter OverviewCHAPTER 2: QUALITY MANAGEMENT,

CONTROL AND ASSURANCECHAPTER 2.1: Introduction to Quality Management,

Control and Assurance

CHAPTER 2.2: The difference between Quality Control and Quality Assurance

CHAPTER 2.3: Quality Control and Quality Assurance in Biotechnology

CHAPTER 2.4: Current Good Manufacturing Practice (cGMP)

Chapter 2.3

Quality Control and Quality Assurance in

Biotechnology

Chapter OverviewCHAPTER 2.3: QUALITY CONTROL AND QUALITY

ASSURANCE IN BIOTECHNOLOGY

CHAPTER 2.3.1: Definition of Quality Control

CHAPTER 2.3.2: Four Common Quality Control Misconceptions

CHAPTER 2.3.3: Objectives of Quality Control

CHAPTER 2.3.4: Elements of Quality Control

CHAPTER 2.3.5: Benefits Obtained From Quality Control


ASSURANCE IN BIOTECHNOLOGYCHAPTER 2.3.6: Benefits Obtained Due to Improved Quality

Control Function

CHAPTER 2.3.7: Tools of Quality Control

CHAPTER 2.3.8: Definition of Quality Assurance

CHAPTER 2.3.9: Objectives of Quality Assurance

CHAPTER 2.3.10:


ASSURANCE IN BIOTECHNOLOGY

CHAPTER 2.3.11: How to Build a Successful Quality Assurance Program

CHAPTER 2.3.12: Characteristics of a Successful Quality Assurance Program

CHAPTER 2.1.13: Benefits Obtained From Quality Assurance

CHAPTER 2.1.14: Conclusions

Chapter 2.3.1

Definition of Quality Control

2.3.1: Definition of Quality Control

Some of the important definitions of quality control are enumerated as under:

“Quality control means the recognition and removal of

identifiable causes and defects, and variables from the set

standards”

- J.A. Shubin


Some of the important definitions of quality control are enumerated as under:

“Quality control means the recognition and removal of

identifiable causes and defects, and variables from the set

standards”

— J.A. Shubin


“Quality control includes techniques and systems for the

achievement of the required quality in the articles produced and for the elimination of sub

standard goods.””

—Tome, Simen and HcGill


“Quality control consists of developing, designing, producing, marketing, and servicing products and services with optimum cost-

effectiveness and usefulness, which customers will purchase with

satisfaction.”

— Dr. Koaru Ishikawa


“A system methods for the cost-effective provision of goods or services whose quality is fit for the purchaser’s requirement.”

JIS defined quality control as:

2.3.2: Four Common Quality Control Misconceptions

In understanding quality control, there were four misconceptions that occurred most often.

The four most common misconceptions regarding quality control are:

i. The definition of quality control is too subjective and can therefore not be defined.

ii. Quality control is the responsibility of one person or group within a company.

iii. Quality control is an expense.

iv. Quality control, quality assurance and testing are the same things.


Looking at it this way, the misconception here lies in the fact that there are a variety of factors or perceptions from which to consider.

At the end of the day, the definition of quality control may vary based on the perspective, but it's certainly definable.

If you go on the premise that you can't define it, you're opening yourself up for failure because it then becomes something that can't be measured or controlled.

Define what quality control means for your organization or purpose, so it can be continuously measured and improved.

i. The definition of quality control is too subjective and can therefore not be defined.


Case study after case study shows that quality control has to be incorporated into the fabric of the organization.

The important of controlling quality of the product or services has to be recognized and respected at every level, starting at the top.

Previous case study have proven that too many quality control initiatives in an organization fail because no one thinks it's their responsibility

Even if an organization has an excellent QC Manager or QC Department, the effort can be lost if there's no involvement from others.



It can be agreed upon that quality control activities such as testing and inspections are the responsibility of those within the internal QC unit(s).

However, this does not support the assumption that responsibility is relinquished from all others.

Organization-wide support can make or break any quality control efforts from those deemed directly responsible.

In order to see maximum results from any quality control program or initiative, total buy-in (active support) or involvement from top down is required and not optional.



This is a laborious and the most difficult hurdle facing an organization when recommending a quality control initiative or action.

However, an organization must knows well that incorporating quality control in every process within the organization does not only reduce their risks but their costs as well.

Thus, organization must not be scared to invest in quality control.

Dedicating some resources to avoid a problem is certainly going to be less of an expense than what it's going to cost to put the problem out when it occurs.

Preventative quality control initiative implemented with a solid strategy is worth every penny in the long run.

iii. Quality control is an expense.


Thinking quality control, quality assurance and testing mean the same thing is a common misconception encountered in any organization.

While they may be closely related, they do refer to very specific and separate activities and should therefore be differentiated.

Quality control is a product-oriented set of activities designed to evaluate (measure and control) against pre-defined requirements.

Quality control includes the actions that will verify the product meets or exceeds expectations.



Quality assurance is a process-oriented set of activities related to ensuring continuous and consistent improvement.

Quality assurance is a preventative action that defines the expectations of the process or product.

Quality assurance is the macro-level of quality that defines the strategic intent and guidelines, specifications and standards development.



Testing is a specific example of a quality control activity but they remain separate terms.

While quality control is a set of activities designed to evaluate whether a developed product (new drug substance, pharmaceutical product etc.) meets customer requirements, testing is the process of executing a system with the intent of finding defects.



Testing forms an integral part of quality control:

Quality ControlAlthough testing is an integral part of QC, not all QC activities are testing activities. Code inspections, technical reviews and stage gates are other examples of QC activities

Testing

2.3.2: Four Common Quality Control Misconceptions Stage-Gate Product/ Service Innovation Process:

2.3.2: Four Common Quality Control Misconceptions Summary:

Misconceptions are not uncommon.

However, identifying those that occur most often provides an opportunity for everyone in the organization to be on the same page.

Debunking the four specifically noted in this chapter will lead to a greater understanding of the quality control function within an organization.

Once everyone in the organization can you define what quality control is, the organization can invest in it, everyone then can share in the responsibility and finally the products or services can be measure and control.

2.3.3: Objectives of Quality Control Present era is the ‘Era of Quality’ and in this age of cutt hroat

competition and large scale production, only manufacturer who supplies better quality goods and renders service to-the consumers can survive .

Thus, quality control has become major consideration before establishing an industrial undertaking.

The objectives of implementing quality in the organization are enumerated as under:

1. To establish the desired quality standards which are acceptable to the customers.

2. To discover flaws or variations in the raw materials and the manufacturing processes in order to ensure smooth and uninterrupted production.

2.3.3: Objectives of Quality Control

3. To evaluate the methods and processes of production and suggest further improvements in their functioning.

4. To study and determine the extent of quality deviation in a product during the manufacturing process.

5. To analyze in detail the causes responsible for such deviation.

6. To undertake such steps which are helpful in achieving the desired quality of the product.

Objectives of implementing quality in the organization:

2.3.4: Elements of Quality Control

1. Ethics 2. Integrity 3. Trust 4. Training 5. Teamwork 6. Leadership 7. Communication 8. Recognition

To be successful implementing quality control, an organization must concentrate on the eight key elements:


1. Ethics

The eight key elements of quality control:

The domain of ethics encompasses moral judgments as to what is right and what is wrong.

Ethical judgments affect and are affected by beliefs, assumptions, individual or corporate behaviors, and societal or cultural values.

The element of ethics can be divided into organizational ethics and individual ethics.


1. Ethics


i. Organizational Ethics

ii. Individual Ethics

Organizational ethics establish a business code of ethics that outlines guidelines that all employees are to adhere to in the performance of their work.

Individual ethics include personal rights or wrongs.


2. Integrity


Integrity implies honesty, morals, values, fairness, and adherence to the facts and data.

The characteristic is what customers, whether internal or external customers expect and deserve to receive.

People see the opposite of integrity as duplicity.

Quality control will not work in an atmosphere of duplicity.


3. Trust


Trust is a by-product of integrity and ethical conduct.

Without trust, the framework of quality control cannot be built.

Trust fosters full participation of all members in an organization.

It allows empowerment that encourages pride ownership and it boost commitment.


3. Trust


Trust allows decision making regarding quality control at appropriate levels in the organization, fosters individual risk-taking for continuous improvement and helps to ensure that measurements focus on improvement of process and are not used to contend people.

Trust is essential to ensure customer satisfaction.

So, trust builds the cooperative environment essential for quality control.


4. Training


Training is very important for employees to be highly productive.

Every persons in the organization are wholly responsible for implementing quality control within their departments, and understanding the definition of quality control.

During the creation and formation of quality control program, employees are trained so that they can become effective employees for the company.


5. Teamwork


To become successful in implementing quality control, teamwork also played an important element of it.

With the use of teams, the business will receive quicker and better solutions to problems encountered.

In teams, people feel more comfortable bringing up problems that may occur in the product or service, and can get help from personnel responsible in quality control to find a solution and put into place.


6. Leadership


It is possibly the most important element in quality control.

It appears everywhere in quality control organization.

Leadership requires the quality control manager to provide an inspiring vision, make strategic directions that are understood by all and to instill values that guide subordinates.

For quality control to be successful in the business, the superior must be committed in leading his employees.


6. Leadership


The leader must understand quality control, believe in it and then demonstrate their belief and commitment through their daily practices of quality control.

The leader must makes sure that strategies, philosophies, values and goals or quality control are transmitted down through out the organization to provide focus, clarity and direction.

The key point is that quality control has to be introduced and led by top management.


7. Communication


Starting from foundation to roof of the quality control initiatives, everything is bound by strong mortar of communication.

Communication acts as a vital link between all elements of quality control.

Communication in any quality control program means a common understanding of ideas between the sender and the receiver.


7. Communication


The success of quality control demands communication with and among all the organization members, suppliers and customers.

A quality control manager must keep open airways where employees in the organization can send and receive information about the quality control process.

Communication coupled with the sharing of correct information is vital.

2.3.4: Elements of Quality Control7. Communication

There are three different ways of communication in any quality control process:

A. Downward Communication

This is the dominant form of communication in a quality control organization.

It is achievable through presentations and discussions.

By this the QC manager are able to make the employees clear about quality control.



B. Upward Communication

By this the lower level of employees are able to provide suggestions to upper management of the affects of quality control.

As employees provide insight and constructive criticism, QC managers must listen effectively to correct the situation that comes about through the use of quality control.



B. Upward Communication

This forms a level of trust between managers and subordinates.

This is also similar to empowering communication, where managers keep open ears and listen to others.



C. Sideways Communication

This type of communication is important because it breaks down barriers between quality control departments and other departments.

It also allows quality control personnel to deal with customers and suppliers in a more professional manner.


8. Recognition


Recognition is the last and final element in the entire quality control system.

Employees strive to receive recognition for themselves and their teams.

As employees are recognized, there can be huge changes in self-esteem, productivity, quality and the amount of effort exhorted to the task at hand.

Recognition comes in its best form when it is immediately following an action that an employee has performed.


8. Recognition


Recognition comes in different ways, places and time such as:

i. Ways

It can be by way of personal letter from top management.

Also by award banquets, plaques or trophies.


8. Recognition


ii. Places

Good performers can be recognized in front of departments, on performance boards and also in front of top management.

iii. Time

Recognition can given at any time like in staff meeting or during annual award banquets.

2.3.5: Benefits Obtained From Quality Control

Quality is raised and the number of defective products decreases.

Quality become more uniform and the number of complaints decreases.

Complaints are dealt with more quickly and effective action is take to prevent their recurrence.

Reliability increases, confidence in the product improves and customers trust is obtained.

Benefits obtained when a company implements quality control:

2.3.6: Benefits Obtained Due to Improved Quality Control Function

Improved company return of investment (ROI) through better quality, less scrap, and improved sales.

Enhanced customer satisfaction.

Reduction of cost associated with supporting redundant quality control procedures and systems.

Development of better production plans.

Identification and resolution of conflicts among management objectives

Benefits obtained when a company quality control function improved:

2.3.7: Tools of Quality Control

There are seven basic tools of quality control, which was first emphasized by Kaoru Ishikawa, the father of “quality circles.”

i. Cause-and-effect diagram (also called Ishikawa or fishbone chart):

ii. Check sheet:

Seven basic tools of quality control:

Identifies many possible causes for an effect or problem and sorts ideas into useful categories.

A structured, prepared form for collecting and analyzing data, that can be adapted for a wide variety of purposes.


iii. Control charts:

iv. Histogram:

v. Pareto chart:


Graphs used to study how a process changes over time.

The most commonly used graph for showing frequency distributions, or how often each different value in a set of data occurs.

Shows on a bar graph which factors are more significant.


vi. Scatter diagram:

vii. Stratification:


Graphs pairs of numerical data, one variable on each axis, to look for a relationship.

A technique that separates data gathered from a variety of sources so that patterns can be seen.

Some lists replace “stratification” with “flowchart” or “run chart”.


i. Fishbone diagram:


Also known as Cause–and–Effect Diagram or Ishikawa Diagram.

The fishbone diagram identifies many possible causes for an effect or problem.

It can be used to structure a brainstorming session.

It immediately sorts ideas into useful categories.


i. Fishbone diagram:


When to Use a Fishbone Diagram:

a. When identifying possible causes for a problem.

b. Especially when a team’s thinking tends to fall into ruts.

Materials Needed:

a. Flipchart or whiteboard.

b. Marking pens.

2.3.7: Tools of Quality Controli. Fishbone diagram:

Fishbone Diagram Procedure:

1. Agree on a problem statement (effect). Write it at the center right of the flipchart or whiteboard. Draw a box around it and draw a horizontal arrow running to it.

2. Brainstorm the major categories of causes of the problem. If this is difficult, use generic headings:

Methods Machines (equipment) People (manpower) Materials Measurement Environment



3. Write the categories of causes as branches from the main arrow.

4. Brainstorm all the possible causes of the problem. - Ask: “Why does this happen?”- As each idea is given, the facilitator writes it as a branch from the appropriate category. - Causes can be written in several places if they relate to several categories.



5. Again ask “why does this happen?” about each cause.- Write sub–causes branching off the causes.

- Continue to ask “Why?” and generate deeper levels of causes. - Layers of branches indicate causal relationships.

6. When the group runs out of ideas, focus attention to places on the chart where ideas are few.

2.3.7: Tools of Quality Control Fishbone Diagram Example:

This fishbone diagram was drawn by a manufacturing team to try to understand the source of periodic iron contamination.

The team used the six generic headings to prompt ideas.

Layers of branches show thorough thinking about the causes of the problem.

For example, under the heading “Machines,” the idea “materials of construction” shows four kinds of equipment and then several specific machine numbers.

Note that some ideas appear in two different places. “Calibration” shows up under “Methods” as a factor in the analytical procedure, and also under “Measurement” as a cause of lab error.


ii. Check Sheet:


When to Use a Check Sheet:

a. When data can be observed and collected repeatedly by the same person or at the same location.

b. When collecting data on the frequency or patterns of events, problems, defects, defect location, or defect causes.

c. When collecting data from a production process.

Also called defect concentration diagram.

A check sheet is a structured, prepared from collecting and analyzing data.


ii. Check Sheet:

Check Sheet Procedure:

1. Decide what event or problem will be observed. Develop operational definitions.

2. Decide when data will be collected and for how long.

3. Design the form. Set it up so that data can be recorded simply by making check marks or Xs or similar symbols and so that data do not have to be recopied for analysis.


ii. Check Sheet:

Check Sheet Procedure:

4. Label all spaces on the form.

5. Test the check sheet for a short trial period to be sure it collects the appropriate data and is easy to use.

6. Each time the targeted event or problem occurs, record data on the check sheet.

2.3.7: Tools of Quality Controlii. Check Sheet:

Check Sheet Example:

The figure below shows a check sheet used to collect data on telephone interruptions.


iii. Control Chart:


Also called statistical process control.

The control chart is a graph used to study how a process changes over time.

Data are plotted in time order.

A control chart always has a central line for the average, an upper line for the upper control limit and a lower line for the lower control limit.

These lines are determined from historical data.

By comparing current data to these lines, you can draw conclusions about whether the process variation is consistent (in control) or is unpredictable (out of control, affected by special causes of variation).


iii. Control Chart:


Control charts for variable data are used in pairs.

The top chart monitors the average, or the centering of the distribution of data from the process.

The bottom chart monitors the range, or the width of the distribution.

If your data were shots in target practice, the average is where the shots are clustering, and the range is how tightly they are clustered.

Control charts for attribute data are used singly (alone).


iii. Control Chart:


When to Use a Control Chart:

a. When controlling ongoing processes by finding and correcting problems as they occur.

b. When predicting the expected range of outcomes from a process.

c. When determining whether a process is stable (in statistical control).

d. When analyzing patterns of process variation from special causes (non-routine events) or common causes (built into the process).

e. When determining whether your quality improvement project should aim to prevent specific problems or to make fundamental changes to the process.

2.3.7: Tools of Quality Controliii. Control Chart:

Control Chart Procedure:

1. Choose the appropriate control chart for your data.

2. Determine the appropriate time period for collecting and plotting data.

3. Collect data, construct your chart and analyze the data.

4. Look for “out-of-control signals” on the control chart. When one is identified, mark it on the chart and investigate the cause.

5. Document how you investigated, what you learned, the cause and how it was corrected.


Control Chart Procedure:

6. Continue to plot data as they are generated. As each new data point is plotted, check for new out-of-control signals.

7. When you start a new control chart, the process may be out of control. If so, the control limits calculated from the first 20 points are conditional limits.

8. When you have at least 20 sequential points from a period when the process is operating in control, recalculate control limits.


Out-of-Control Signals:

Figure 1 Control Chart: Out-of-Control Signals


Out-of-Control Signals:

A single point outside the control limits. In Figure 1, point sixteen is above the UCL (upper control limit).

Two out of three successive points are on the same side of the centerline and farther than 2 σ from it. In Figure 1, point 4 sends that signal.

Four out of five successive points are on the same side of the centerline and farther than 1 σ from it. In Figure 1, point 11 sends that signal.

A run of eight in a row are on the same side of the centerline. Or 10 out of 11, 12 out of 14 or 16 out of 20. In Figure 1, point 21 is eighth in a row above the centerline.

Obvious consistent or persistent patterns that suggest something unusual about your data and your process.


iv. Histogram:


A frequency distribution shows how often each different value in a set of data occurs.

A histogram is the most commonly used graph to show frequency distributions.

It looks very much like a bar chart, but there are important differences between them.


iv. Histogram:


When to Use a Histogram:

a. When the data are numerical.

b. When you want to see the shape of the data’s distribution, especially when determining whether the output of a process is distributed approximately normally.

c. When analyzing whether a process can meet the customer’s requirements.

d. When analyzing what the output from a supplier’s process looks like.


iv. Histogram:


When to Use a Histogram:

e. When seeing whether a process change has occurred from one time period to another.

f. When determining whether the outputs of two or more processes are different.

g. When you wish to communicate the distribution of data quickly and easily to others.

2.3.7: Tools of Quality Controliv. Histogram:

Histogram Procedure:

1. Collect at least 50 consecutive data points from a process.

2. Use the histogram worksheet to set up the histogram. It will help you determine the number of bars, the range of numbers that go into each bar and the labels for the bar edges.

3. After calculating W in step 2 of the worksheet, use your judgment to adjust it to a convenient number. For example, you might decide to round 0.9 to an even 1.0. The value for W must not have more decimal places than the numbers you will be graphing.


Histogram Worksheet:


Histogram Procedure:

4. Draw x- and y-axes on graph paper. Mark and label the y-axis for counting data values. Mark and label the x-axis with the L values from the worksheet. The spaces between these numbers will be the bars of the histogram. Do not allow for spaces between bars.

5. For each data point, mark off one count above the appropriate bar with an X or by shading that portion of the bar.

2.3.7: Tools of Quality Controlv. Pareto Chart:

Also called Pareto diagram or Pareto analysis.

A Pareto chart is a bar graph.

The lengths of the bars represent frequency or cost (time or money), and are arranged with longest bars on the left and the shortest to the right. In this way the chart visually depicts which situations are more significant.

When to Use a Pareto Chart:

a. When analyzing data about the frequency of problems or causes in a process.

b. When there are many problems or causes and you want to focus on the most significant.


v. Pareto Chart:


When to Use a Pareto Chart:

c. When analyzing broad causes by looking at their specific components.

d. When communicating with others about your data.

Pareto Chart Procedure:

1. Decide what categories you will use to group items.

2. Decide what measurement is appropriate. Common measurements are frequency, quantity, cost and time.


v. Pareto Chart:



3. Decide what period of time the Pareto chart will cover: One work cycle? One full day? A week?

4. Collect the data, recording the category each time (Or assemble data that already exist).

5. Subtotal the measurements for each category.

6. Determine the appropriate scale for the measurements you have collected. The maximum value will be the largest subtotal from step 5. (If you will do optional steps 8 and 9 below, the maximum value will be the sum of all subtotals from step 5.) Mark the scale on the left side of the chart.


v. Pareto Chart:



7. Construct and label bars for each category. Place the tallest at the far left, then the next tallest to its right and so on. If there are many categories with small measurements, they can be grouped as “other.”

8. Calculate the percentage for each category: the subtotal for that category divided by the total for all categories. Draw a right vertical axis and label it with percentages. Be sure the two scales match: For example, the left measurement that corresponds to one-half should be exactly opposite 50% on the right scale.


v. Pareto Chart:



9. Calculate and draw cumulative sums: Add the subtotals for the first and second categories, and place a dot above the second bar indicating that sum. To that sum add the subtotal for the third category, and place a dot above the third bar for that new sum. Continue the process for all the bars. Connect the dots, starting at the top of the first bar. The last dot should reach 100 percent on the right scale.

*Steps 8 and 9 are optional but are useful for analysis and communication.

2.3.7: Tools of Quality Control Seven basic tools of quality control:

Pareto Chart Examples:

Example #1 shows how many customer complaints were received in each of five categories.

Example #1

2.3.7: Tools of Quality Control Pareto Chart Examples:

Example #2 takes the largest category, “documents,” from Example #1, breaks it down into six categories of document-related complaints, and shows cumulative values.

If all complaints cause equal distress to the customer, working on eliminating document-related complaints would have the most impact, and of those, working on quality certificates should be most fruitful

Example #2

2.3.7: Tools of Quality Controlvi. Scatter Diagram:

Also called the scatter plot or X–Y graph.

The scatter diagram graphs pairs of numerical data, with one variable on each axis, to look for a relationship between them.

If the variables are correlated, the points will fall along a line or curve. The better the correlation, the tighter the points will hug the line.

When to Use a Scatter Diagram:

a. When you have paired numerical data.

b. When your dependent variable may have multiple values for each value of your independent variable.


When to Use a Scatter Diagram:

c. When trying to determine whether the two variables are related, such as:

When trying to identify potential root causes of problems.

After brainstorming causes and effects using a fishbone diagram, to determine objectively whether a particular cause and effect are related.

When determining whether two effects that appear to be related both occur with the same cause.

When testing for autocorrelation before constructing a control chart.


Scatter Diagram Procedure:

1. Collect pairs of data where a relationship is suspected.

2. Draw a graph with the independent variable on the horizontal axis and the dependent variable on the vertical axis. For each pair of data, put a dot or a symbol where the x-axis value intersects the y-axis value (If two dots fall together, put them side by side, touching, so that you can see both).

3. Look at the pattern of points to see if a relationship is obvious. If the data clearly form a line or a curve, you may stop. The variables are correlated. You may wish to use regression or correlation analysis now. (Otherwise, complete steps 4 through 7).



4. Divide points on the graph into four quadrants. If there are X points on the graph, Count X/2 points from top to bottom and draw a horizontal line. Count X/2 points from left to right and draw a vertical line. If number of points is odd, draw the line through the middle point.

5. Count the points in each quadrant. Do not count points on a line.

6. Add the diagonally opposite quadrants. Find the smaller sum and the total of points in all quadrants.

A = points in upper left + points in lower right B = points in upper right + points in lower left Q = the smaller of A and B N = A + B



7. Look up the limit for N on the trend test table. If Q is less than the limit, the two variables are related. If Q is greater than or equal to the limit, the pattern

could have occurred from random chance.

chapter 2.3 quality control and assurance in biotechnology

Documents

understanding quality

quality management

required quality

bnn40703 quality assurance

chapter overview chapter

biotechnology chapter

common misconceptions

removal of identifiable